Substituted 2-oxy-quinoline-3-carboxamides as KCNQ2/3 modulators

ABSTRACT

The invention relates to substituted 2-oxy-quinoline-3-carboxamides, to pharmaceutical compositions containing these compounds and also to these compounds for use in the treatment and/or prophylaxis of pain and further diseases and/or disorders.

This application is a divisional of U.S. patent application Ser. No.13/218,512, filed Aug. 26, 2011, now pending, which claims priority ofU.S. Provisional Application No. 61/377,510, filed on Aug. 27, 2010 andEuropean Application No. 10 008 921.8 filed Aug. 27, 2010, the entirecontents of which are incorporated herein by reference.

The invention relates to substituted 2-oxy-quinoline-3-carboxamides, topharmaceutical compositions containing these compounds and also to thesecompounds for use in the treatment and/or prophylaxis of pain andfurther diseases and/or disorders.

The treatment of pain, in particular of neuropathic pain, is of greatimportance in medicine. There is a worldwide need for effective paintherapies. The urgent need for action for a target-orientated treatmentof chronic and non-chronic states of pain appropriate for the patient,by which is to be understood the successful and satisfactory treatmentof pain for the patient, is also documented in the large number ofscientific works which have recently been published in the field ofapplied analgesics and of fundamental research into nociception.

A pathophysiological feature of chronic pain is the overexcitability ofneurons. Neuronal excitability is influenced decisively by the activityof K⁺ channels, since these determine decisively the resting membranepotential of the cell and therefore the excitability threshold.Heteromeric K⁺ channels of the molecular subtype KCNQ2/3 (Kv7.2/7.3) areexpressed in neurons of various regions of the central (hippocampus,amygdala) and peripheral (dorsal root ganglia) nervous system andregulate the excitability thereof. Activation of KCNQ2/3 K⁺ channelsleads to a hyperpolarization of the cell membrane and, accompanyingthis, to a decrease in the electrical excitability of these neurons.KCNQ2/3-expressing neurons of the dorsal root ganglia are involved inthe transmission of nociceptive stimuli from the periphery into thespinal marrow (Passmore et al., J. Neurosci. 2003; 23(18): 7227-36).

It has accordingly been possible to detect an analgesic activity inpreclinical neuropathy and inflammatory pain models for the KCNQ2/3agonist retigabine (Blackburn-Munro and Jensen, Eur J. Pharmacol. 2003;460(2-3); 109-16; post et al., Naunyn Schmiedebergs Arch Pharmacol 2004;369(4): 382-390).

The KCNQ2/3 K⁺ channel thus represents a suitable starting point for thetreatment of pain; in particular of pain selected from the groupconsisting of chronic pain, acute pain, neuropathic pain, inflammatorypain, visceral pain and muscular pain (Nielsen et al., Eur J Pharmacol.2004; 487(1-3): 93-103), in particular of neuropathic and inflammatorypain. Moreover, the KCNQ2/3 K⁺ channel is a suitable target for therapyof a large number of further diseases, such as, for example, migraine(US2002/0128277), cognitive diseases (Gribkoff, Expert Opin Ther Targets2003; 7(6): 737-748), anxiety (Korsgaard et al., J Pharmacol Exp Ther.2005, 14(1): 282-92), epilepsy (Wickenden et al., Expert Opin Ther Pat2004; 14(4): 457-469; Gribkoff, Expert Opin Ther Targets 2008, 12(5):565-81; Miceli et al., Curr Opin Pharmacol 2008, 8(1): 65-74), urinaryincontinence (Streng et al., J Urol 2004; 172: 2054-2058), dependency(Hansen et al., Eur J Pharmacol 2007, 570(1-3): 77-88), mania/bipolardisorders (Dencker et al., Epilepsy Behav 2008, 12(1): 49-53) anddystonia-associated dyskinesias (Richter et al., Br J Pharmacol 2006,149(6): 747-53).

Substituted quinolines and other compounds are known from e.g. FR 2 532939, WO 2010/094644, WO 2010/094645, WO 2008/007211, WO 2008/050199, andEP 0 089 597.

Substituted compounds that have an affinity for the KCNQ2/3 K⁺ channelare e.g. known from the prior art (WO 2008/046582, WO 2010/046108).Substituted sulfonyl urea compounds are e.g. known from EP 0 089 597 A2.Heterocyclic modulators of TGR5 are e.g. known from WO 2008/097976 A1.

There is a demand for further compounds having comparable or betterproperties, not only with regard to affinity to KCNQ2/3 K⁺ channels perse (potency, efficacy).

Thus, it may be advantageous to improve the metabolic stability, thesolubility in aqueous media or the permeability of the compounds. Thesefactors can have a beneficial effect on oral bioavailability or canalter the PK/PD (pharmacokinetic/pharmacodynamic) profile; this can leadto a more beneficial period of effectiveness, for example. A weak ornon-existent interaction with transporter molecules, which are involvedin the ingestion and the excretion of pharmaceutical compositions, isalso to be regarded as an indication of improved bioavailability and atmost low interactions of pharmaceutical compositions. Furthermore, theinteractions with the enzymes involved in the decomposition and theexcretion of pharmaceutical compositions should also be as low aspossible, as such test results also suggest that at most lowinteractions, or no interactions at all, of pharmaceutical compositionsare to be expected.

In addition, it may be advantageous if the compounds show a highselectivity towards other receptors of the KCNQ family (specificity),e.g. towards KCNQ1, KCNQ3/5 or KCNQ4. A high selectivity may have apositive effect on the side effects profile: for example it is knownthat compounds which (also) have an affinity to KCNQ1 are likely to havea potential for cardial side effects. Therefore, a high selectivitytowards KCNQ1 may be desirable. However, it may also be advantageous forthe compounds to show a high selectivity towards other receptors. Forinstance, it may be advantageous for the compounds to show a lowaffinity for the hERG ion channel or the L-type calcium ion channel(phenylalkylamine-, benzothiazepin-, dihydropyridine-binding site) sincethese receptors are known to possibly have a potential for cardial sideeffects. Further, an improved selectivity towards binding to otherendogenic proteins (i.e. receptors or enzymes) may result in a betterside effects profile and, consequently to an improved tolerance.

It was therefore an object of the invention to provide new compoundshaving advantages over the compounds of the prior art. These compoundsshould be suitable in particular as pharmacological active ingredientsin pharmaceutical compositions, preferably in pharmaceuticalcompositions for the treatment and/or prophylaxis of disorders and/ordiseases which are mediated, at least in part, by KCNQ2/3 K⁺ channels.

That object is achieved by the subject-matter of the patent claims.

It has been found, surprisingly, that substituted compounds of thegeneral formula (I) given below are suitable for the treatment of pain.It has also been found, surprisingly, that substituted compounds of thegeneral formula (I) given below also have an excellent affinity for theKCNQ2/3 K⁺ channel and are therefore suitable for the prophylaxis and/ortreatment of disorders and/or diseases that are mediated at least inpart by KCNQ2/3 K⁺ channels. The substituted compounds thereby act asmodulators, i.e. agonists or antagonists, of the KCNQ2/3 K⁺ channel.

The present invention therefore relates to a substituted compound ofgeneral formula (I),

wherein

-   R¹ represents a C₁₋₁₀-aliphatic residue, unsubstituted or mono- or    polysubstituted; a C₃₋₁₀-cycloaliphatic residue or a 3 to 10    membered heterocycloaliphatic residue, in each case unsubstituted or    mono- or polysubstituted and in each case optionally bridged via a    C₁₋₈ aliphatic group, which in turn may be unsubstituted or mono- or    polysubstituted; aryl or heteroaryl, in each case unsubstituted or    mono- or polysubstituted and in each case optionally bridged via a    C₁₋₈ aliphatic group, which in turn may be unsubstituted or mono- or    polysubstituted;-   R² represents H; F; Cl; Br; I; CN; CF₃; C(═O)H; NO₂; OCF₃; SCF₃; a    C₁₋₄-aliphatic residue, a C(═O)—C₁₋₄ aliphatic residue, a    C(═O)—O—C₁₋₄ aliphatic residue, a C(═O)—NH—C₁₋₄ aliphatic residue, a    C(═O)—N(C₁₋₄ aliphatic residue)₂, wherein the C₁₋₄ aliphatic residue    may be in each case be unsubstituted or mono- or polysubstituted; a    O—C₁₋₄-aliphatic residue, a O—C(═O)—C₁₋₄-aliphatic residue, a    S—C₁₋₄-aliphatic residue, a S(═O)₂—C₁₋₄-aliphatic residue, a    S(═O)₂—O—C₁₋₄-aliphatic residue, wherein the C₁₋₄ aliphatic residue    may be in each case be unsubstituted or mono- or polysubstituted; a    C₃₋₆-cycloaliphatic residue or a 3 to 6 membered    heterocycloaliphatic residue, in each case unsubstituted or mono- or    polysubstituted and in each case optionally bridged via a C₁₋₄    aliphatic group, which in turn may be unsubstituted or mono- or    polysubstituted;-   R³, R⁴, R⁵ and R⁶ each independently of one another represent H; F;    Cl; Br; I; CN; OF₃; C(═O)H; C(═O)—OH; C(═O)—NH₂; SCF₃; S(═O)₂—OH;    NO₂; OCF₃; a C₁₋₄-aliphatic residue, a C(═O)—C₁₋₄ aliphatic residue,    a C(═O)—O—C₁₋₄ aliphatic residue, a C(═O)—NH—C₁₋₄ aliphatic residue,    a C(═O)—N(C₁₋₄ aliphatic residue)₂, wherein the C₁₋₄ aliphatic    residue may be in each case be unsubstituted or mono- or    polysubstituted; a O—C₁₋₄-aliphatic residue, a    O—C(═O)—C₁₋₄-aliphatic residue, a S—C₁₋₄-aliphatic residue, a    S(═O)₂—C₁₋₄-aliphatic residue, a S(═O)₂—O—C₁₋₄-aliphatic residue,    wherein the C₁₋₄ aliphatic residue may be in each case be    unsubstituted or mono- or polysubstituted; a NH(C₁₋₄ aliphatic    residue), a N(C₁₋₄ aliphatic residue)₂, a NH—C(═O)—C₁₋₄ aliphatic    residue, a NH—S(═O)₂—C₁₋₄-aliphatic residue, a N(C₁₋₄ aliphatic    residue)-C(═O)—C₁₋₄ aliphatic residue, or a N(C₁₋₄ aliphatic    residue)-S(═O)₂—C₁₋₄ aliphatic residue, wherein the C₁₋₄ aliphatic    residue may in each case be unsubstituted or mono- or    polysubstituted; a C₃₋₆-cycloaliphatic residue or a 3 to 6 membered    heterocycloaliphatic residue, in each case unsubstituted or mono- or    polysubstituted and in each case optionally bridged via a C₁₋₄    aliphatic group, which in turn may be unsubstituted or mono- or    polysubstituted;-   R⁷ represents a C₁₋₁₀-aliphatic residue, unsubstituted or mono- or    polysubstituted; a C₃₋₁₀-cycloaliphatic residue or a 3 to 10    membered heterocycloaliphatic residue, in each case unsubstituted or    mono- or polysubstituted and in each case optionally bridged via a    C₁₋₈ aliphatic group, which in turn may be unsubstituted or mono- or    polysubstituted;    -   on the condition that if R⁷ denotes a 3 to 10 membered        heterocycloaliphatic residue, the 3 to 10 membered        heterocycloaliphatic residue is linked via a carbon atom,        in which an “aliphatic group” and “aliphatic residue” can in        each case be branched or unbranched, saturated or unsaturated,        in which a “cycloaliphatic residue” and a “heterocycloaliphatic        residue” can in each case be saturated or unsaturated,        in which “mono- or polysubstituted” with respect to an        “aliphatic group” and an “aliphatic residue” relates, with        respect to the corresponding residues or groups, to the        substitution of one or more hydrogen atoms each independently of        one another by at least one substituent selected from the group        consisting of F, Cl, Br, I, NO₂, NH₂, an NH(C₁₋₄ aliphatic        residue), an N(C₁₋₄ aliphatic residue)₂, a NH—C(═O)—C₁₋₄        aliphatic residue, a NH—S(═O)₂—C₁₋₄ aliphatic residue, ═O, OH,        OCF₃, a O—C₁₋₄-aliphatic residue, a O—C(═O)—C₁₋₄-aliphatic        residue, SH, SCF₃, a S—C₁₋₄-aliphatic residue, S(═O)₂OH, a        S(═O)₂—C₁₋₄-aliphatic residue, a S(═O)₂—O—C₁₋₄-aliphatic        residue, a S(═O)₂—NH—C₁₋₄-aliphatic residue, CN, CF₃, CHO, COOH,        a C₁₋₄-aliphatic residue, a C(═O)—C₁₋₄-aliphatic residue, a        C(═O)—O—C₁₋₄-aliphatic residue, a C₃₋₆-cycloaliphatic residue, a        3 to 6 membered heterocycloaliphatic residue, C(═O)—NH₂, a        C(═O)—NH(C₁₋₄ aliphatic residue), and a C(═O)—N(C₁₋₄ aliphatic        residue)₂;        in which “mono- or polysubstituted” with respect to a        “cycloaliphatic residue” and a “heterocycloaliphatic residue”        relates, with respect to the corresponding residues, to the        substitution of one or more hydrogen atoms each independently of        one another by at least one substituent selected from the group        consisting of F, Cl, Br, I, NO₂, NH₂, an NH(C₁₋₄ aliphatic        residue), an N(C₁₋₄ aliphatic residue)₂, a NH—C(═O)—C₁₋₄        aliphatic residue, a NH—S(═O)₂—C₁₋₄ aliphatic residue, ═O, OH,        OCF₃, a O—C₁₋₄-aliphatic residue, a O—C(═O)—C₁₋₄-aliphatic        residue, SH, SCF₃, a S—C₁₋₄-aliphatic residue, S(═O)₂OH, a        S(═O)₂—C₁₋₄-aliphatic residue, a S(═O)₂—O—C₁₋₄-aliphatic        residue, a S(═O)₂—NH—C₁₋₄-aliphatic residue, CN, CF₃, CHO, COOH,        a C₁₋₄-aliphatic residue, a C(═O)—C₁₋₄-aliphatic residue, a        C(═O)—O—C₁₋₄-aliphatic residue, a C₃₋₆-cycloaliphatic residue, a        3 to 6 membered heterocycloaliphatic residue, C(═O)—NH₂, a        C(═O)—NH(C₁₋₄ aliphatic residue), and a C(═O)—N(C₁₋₄ aliphatic        residue)₂;        in which “mono- or polysubstituted” with respect to “aryl” and a        “heteroaryl” relates, with respect to the corresponding        residues, to the substitution of one or more hydrogen atoms each        independently of one another by at least one substituent        selected from the group        consisting of F, Cl, Br, I, NO₂, NH₂,

an NH(C₁₋₄ aliphatic residue), an N(C₁₋₄ aliphatic residue)₂, anNH—C(═O)—C₁₋₄ aliphatic residue, an NH—S(═O)₂—C₁₋₄ aliphatic residue,OH, OCF₃, a O—C₁₋₄-aliphatic residue, a O—C(═O)—C₁₋₄-aliphatic residue,SH, SCF₃, a S—C₁₋₄-aliphatic residue, S(═O)₂OH, a S(═O)₂—C₁₋₄-aliphaticresidue, a S(═O)₂—O—C₁₋₄-aliphatic residue, a S(═O)₂—NH—C₁₋₄-aliphaticresidue, CN, CF₃, C(═O)H, C(═O)OH, a C₁₋₄-aliphatic residue, aC(═O)—C₁₋₄-aliphatic residue, a C(═O)—O—C₁₋₄-aliphatic residue, aC₃₋₆-cycloaliphatic residue, a 3 to 6 membered heterocycloaliphaticresidue, benzyl, aryl, heteroaryl, C(═O)—NH₂, a C(═O)—NH(C₁₋₄ aliphaticresidue), and a C(═O)—N(C₁₋₄ aliphatic residue)₂;in the form of the free compounds, the racemate, the enantiomers,diastereomers, mixtures of the enantiomers or diastereomers in anymixing ratio, or of an individual enantiomer or diastereomer, or in theform of the salts of physiologically acceptable acids or bases, or inthe form of the solvates, in particular hydrates.

The terms “C₁₋₁₀-aliphatic residue”, “C₁₋₈-aliphatic residue”,“C₁₋₆-aliphatic residue” and “C₁₋₄-aliphatic residue” and“C₁₋₂-aliphatic residue” comprise in the sense of this invention acyclicsaturated or unsaturated aliphatic hydrocarbon residues, which can bebranched or unbranched and also unsubstituted or mono- orpolysubstituted, containing 1 to 10, or 1 to 8, or 1 to 6, or 1 to 4 or1 to 2 carbon atoms, respectively, i.e. C₁₋₁₀ alkanyls, C₂₋₁₀ alkenylsand C₂₋₁₀ alkynyls as well as C₁₋₈ alkanyls, C₂₋₈ alkenyls and C₂₋₈alkynyls as well as C₁₋₆ alkanyls, C₂₋₆ alkenyls and C₂₋₆ alkynyls aswell as C₁₋₄ alkanyls, C₂₋₄ alkenyls and C₂₋₄ alkynyls, as well as C₁₋₂alkanyls, C₂-alkenyls and C₂ alkynyls, respectively. In this case,alkenyls comprise at least one C—C double bond (a C═C-bond) and alkynylscomprise at least one C—C triple bond (a C≡C-bond). Preferably,aliphatic residues are selected from the group consisting of alkanyl(alkyl) and alkenyl residues, more preferably are alkanyl residues.Preferred C₁₋₁₀ alkanyl residues are selected from the group consistingof methyl, ethyl, n-propyl, 2-propyl, n-butyl, isobutyl, sec.-butyl,tert.-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, n-heptyl, n-octyl,n-nonyl and n-decyl. Preferred C₁₋₈ alkanyl residues are selected fromthe group consisting of methyl, ethyl, n-propyl, 2-propyl, n-butyl,isobutyl, sec.-butyl, tert.-butyl, n-pentyl, isopentyl, neopentyl,n-hexyl, n-heptyl and n-octyl. Preferred C₁₋₆ alkanyl residues areselected from the group consisting of methyl, ethyl, n-propyl, 2-propyl,n-butyl, isobutyl, sec.-butyl, tert.-butyl, n-pentyl, isopentyl,neopentyl and n-hexyl. Preferred C₁₋₄ alkanyl residues are selected fromthe group consisting of methyl, ethyl, n-propyl, 2-propyl, n-butyl,isobutyl, sec.-butyl and tert.-butyl. Preferred C₂₋₁₀ alkenyl residuesare selected from the group consisting of ethenyl (vinyl), propenyl(—CH₂CH═CH₂, —CH═CH—CH₃, —C(═CH₂)—CH₃), butenyl, pentenyl, hexenylheptenyl, octenyl, nonenyl and decenyl. Preferred C₂₋₈ alkenyl residuesare selected from the group consisting of ethenyl (vinyl), propenyl(—CH₂CH═CH₂, —CH═CH—CH₃, —C(═CH₂)—CH₃), butenyl, pentenyl, hexenylheptenyl and octenyl. Preferred C₂₋₆ alkenyl residues are selected fromthe group consisting of ethenyl (vinyl), propenyl (—CH₂CH═CH₂,—CH═CH—CH₃, —C(═CH₂)—CH₃), butenyl, pentenyl and hexenyl. Preferred C₂₋₄alkenyl residues are selected from the group consisting of ethenyl(vinyl), propenyl (—CH₂CH═CH₂, —CH═CH—CH₃, —C(═CH₂)—CH₃) and butenyl.Preferred C₂₋₁₀ alkynyl residues are selected from the group consistingof ethynyl, propynyl (—CH₂—C≡CH, —C≡C—CH₃), butynyl, pentynyl, hexynyl,heptynyl, octynyl, nonynyl and decynyl. Preferred C₂₋₈ alkynyl residuesare selected from the group consisting of ethynyl, propynyl (—CH₂—C≡CH,—C≡C—CH₃), butynyl, pentynyl, hexynyl, heptynyl and octynyl. PreferredC₂₋₆ alkynyl residues are selected from the group consisting of ethynyl,propynyl (—CH₂—C≡CH, —C≡C—CH₃), butynyl, pentynyl and hexynyl PreferredC₂₋₄ alkynyl residues are selected from the group consisting of ethynyl,propynyl (—CH₂—C≡CH, —C≡C—CH₃) and butynyl.

The terms “C₃₋₆-cycloaliphatic residue” and “C₃₋₁₀-cycloaliphaticresidue” mean for the purposes of this invention cyclic aliphatichydrocarbons containing 3, 4, 5 or 6 carbon atoms and 3, 4, 5, 6, 7, 8,9 or 10 carbon atoms, respectively, wherein the hydrocarbons in eachcase can be saturated or unsaturated (but not aromatic), unsubstitutedor mono- or polysubstituted. The cycloaliphatic residues can be bound tothe respective superordinate general structure via any desired andpossible ring member of the cycloaliphatic residue. The cycloaliphaticresidues can also be condensed with further saturated, (partially)unsaturated, (hetero)cyclic, aromatic or heteroaromatic ring systems,i.e. with cycloaliphatic, heterocycloaliphatic, aryl or heteroarylresidues which can in turn be unsubstituted or mono- or polysubstituted.C₃₋₁₀ cycloaliphatic residue can furthermore be singly or multiplybridged such as, for example, in the case of adamantyl,bicyclo[2.2.1]heptyl or bicyclo[2.2.2]octyl. Preferred C₃₋₁₀cycloaliphatic residues are selected from the group consisting ofcyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl,cyclooctyl, cyclononyl, cyclodecyl, adamantyl,

cyclopentenyl, cyclohexenyl, cycloheptenyl and cyclooctenyl. PreferredC₃₋₆ cycloaliphatic residues are selected from the group consisting ofcyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopentenyl andcyclohexenyl.

The terms “3-6-membered heterocycloaliphatic residue” and “3-10-memberedheterocycloaliphatic residue” mean for the purposes of this inventionheterocycloaliphatic saturated or unsaturated (but not aromatic)residues having 3-6, i.e. 3, 4, 5 or 6 ring members, and 3-10, i.e. 3,4, 5, 6, 7, 8, 9 or 10 ring members, respectively, in which in each caseat least one, if appropriate also two or three carbon atoms are replacedby a heteroatom or a heteroatom group each selected independently of oneanother from the group consisting of O, S, S(═O)₂, N, NH and N(C₁₋₈alkyl), preferably N(CH₃), wherein the ring members can be unsubstitutedor mono- or polysubstituted. The heterocycloaliphatic residue can bebound to the superordinate general structure via any desired andpossible ring member of the heterocycloaliphatic residue. Theheterocycloaliphatic residues can also be condensed with furthersaturated, (partially) unsaturated (hetero)cycloaliphatic or aromatic orheteroaromatic ring systems, i.e. with cycloaliphatic,heterocycloaliphatic, aryl or heteroaryl residues, which can in turn beunsubstituted or mono- or polysubstituted. Preferredheterocycloaliphatic residues are selected from the group consisting ofazetidinyl, aziridinyl, azepanyl, azocanyl, diazepanyl, dithiolanyl,dihydroquinolinyl, dihydropyrrolyl, dioxanyl, dioxolanyl, dioxepanyl,dihydroindenyl, dihydropyridinyl, dihydrofuranyl, dihydroisoquinolinyl,dihydroindolinyl, dihydroisoindolyl, imidazolidinyl, isoxazolidinyl,morpholinyl, oxiranyl, oxetanyl, pyrrolidinyl, piperazinyl,4-methylpiperazinyl, piperidinyl, pyrazolidinyl, pyranyl,tetrahydropyrrolyl, tetrahydropyranyl, tetrahydroquinolinyl,tetrahydroisoquinolinyl, tetrahydroindolinyl, tetrahydrofuranyl,tetrahydropyridinyl, tetrahydrothiophenyl, tetrahydropyridoindolyl,tetrahydronaphthyl, tetrahydrocarbolinyl, tetrahydroisoxazolo-pyridinyl,thiazolidinyl and thiomorpholinyl.

The term “aryl” means for the purpose of this invention aromatichydrocarbons having 6 to 14 ring members, including phenyls andnaphthyls. Each aryl residue can be unsubstituted or mono- orpolysubstituted, wherein the aryl substituents can be the same ordifferent and in any desired and possible position of the aryl. The arylcan be bound to the superordinate general structure via any desired andpossible ring member of the aryl residue. The aryl residues can also becondensed with further saturated, (partially) unsaturated,(hetero)cycloaliphatic, aromatic or heteroaromatic ring systems, i.e.with a cycloaliphatic, heterocycloaliphatic, aryl or heteroaryl residue,which can in turn be unsubstituted or mono- or polysubstituted. Examplesof condensed aryl residues are benzodioxolanyl and benzodioxanyl.Preferably, aryl is selected from the group consisting of phenyl,1-naphthyl, 2-naphthyl, fluorenyl and anthracenyl, each of which can berespectively unsubstituted or mono- or polysubstituted. A particularlypreferred aryl is phenyl, unsubstituted or mono- or polysubstituted.

The term “heteroaryl” for the purpose of this invention represents a 5or 6-membered cyclic aromatic residue containing at least 1, ifappropriate also 2, 3, 4 or 5 heteroatoms, wherein the heteroatoms areeach selected independently of one another from the group S, N and O andthe heteroaryl residue can be unsubstituted or mono- or polysubstituted;in the case of substitution on the heteroaryl, the substituents can bethe same or different and be in any desired and possible position of theheteroaryl. The binding to the superordinate general structure can becarried out via any desired and possible ring member of the heteroarylresidue. The heteroaryl can also be part of a bi- or polycyclic systemhaving up to 14 ring members, wherein the ring system can be formed withfurther saturated, (partially) unsaturated, (hetero)cycloaliphatic oraromatic or heteroaromatic rings, i.e. with a cycloaliphatic,heterocycloaliphatic, aryl or heteroaryl residue, which can in turn beunsubstituted or mono- or polysubstituted. It is preferable for theheteroaryl residue to be selected from the group consisting ofbenzofuranyl, benzoimidazolyl, benzothienyl, benzothiadiazolyl,benzothiazolyl, benzotriazolyl, benzooxazolyl, benzooxadiazolyl,quinazolinyl, quinoxalinyl, carbazolyl, quinolinyl, dibenzofuranyl,dibenzothienyl, furyl (furanyl), imidazolyl, imidazothiazolyl,indazolyl, indolizinyl, indolyl, isoquinolinyl, isoxazoyl, isothiazolyl,indolyl, naphthyridinyl, oxazolyl, oxadiazolyl, phenazinyl,phenothiazinyl, phthalazinyl, pyrazolyl, pyridyl (2-pyridyl, 3-pyridyl,4-pyridyl), pyrrolyl, pyridazinyl, pyrimidinyl, pyrazinyl, purinyl,phenazinyl, thienyl (thiophenyl), triazolyl, tetrazolyl, thiazolyl,thiadiazolyl and triazinyl. Furyl, pyridyl, oxazolyl, thiazolyl andthienyl are particularly preferred.

The terms “aryl, heteroaryl, a heterocycloaliphatic residue, or acycloaliphatic residue bridged via a C₁₋₄-aliphatic group or via aC₁₋₈-aliphatic group” mean for the purpose of the invention that theexpressions “aryl, heteroaryl, heterocycloaliphatic residue andcycloaliphatic residue” have the above-defined meanings and are bound tothe respective superordinate general structure via a C₁₋₄-aliphaticgroup or via a C₁₋₈-aliphatic group, respectively. The C₁₋₄ aliphaticgroup and the C₁₋₈-aliphatic group can in all cases be branched orunbranched, unsubstituted or mono- or polysubstituted. The C₁₋₄aliphatic group can in all cases be furthermore saturated orunsaturated, i.e. can be a C₁₋₄ alkylene group, a C₂₋₄ alkenylene groupor a C₂₋₄ alkynylene group. The same applies to a C₁₋₈-aliphatic group,i.e. a C₁₋₈-aliphatic group can in all cases be furthermore saturated orunsaturated, i.e. can be a C₁₋₈ alkylene group, a C₂₋₈ alkenylene groupor a C₂₋₈ alkynylene group. Preferably, the C₁₋₄-aliphatic group is aC₁₋₄ alkylene group or a C₂₋₄ alkenylene group, more preferably a C₁₋₄alkylene group. Preferably, the C₁₋₈-aliphatic group is a C₁₋₈ alkylenegroup or a C₂₋₈ alkenylene group, more preferably a C₁₋₈ alkylene group.Preferred C₁₋₄ alkylene groups are selected from the group consisting of—CH₂—, —CH₂—CH₂—, —CH(CH₃)—, —CH₂—CH₂—CH₂—, —CH(CH₃)—CH₂—, —CH(CH₂CH₃)—,—CH₂—(CH₂)₂—CH₂—, —CH(CH₃)—CH₂—CH₂—, —CH₂—CH(CH₃)—CH₂—,—CH(CH₃)—CH(CH₃)—, —CH(CH₂CH₃)—CH₂—, —C(CH₃)₂—CH₂—, —CH(CH₂CH₂CH₃)— and—C(CH₃)(CH₂CH₃)—. Preferred C₂₋₄ alkenylene groups are selected from thegroup consisting of —CH═CH—, —CH═CH—CH₂—, —C(CH₃)═CH₂—, —CH═CH—CH₂—CH₂—,—CH₂—CH═CH—CH₂—, —CH═CH—CH═CH—, —C(CH₃)═CH—CH₂—, —CH═C(CH₃)—CH₂—,—C(CH₃)═C(CH₃)— and —C(CH₂CH₃)═CH—. Preferred C₂₋₄ alkynylene groups areselected from the group consisting of —C≡C—, —C≡C—CH₂—, —C≡C—CH₂—CH₂—,—C≡C—CH(CH₃)—, —CH₂—C≡C—CH₂— and —C≡C—C≡C—. Preferred C₁₋₈ alkylenegroups are selected from the group consisting of —CH₂—, —CH₂—CH₂—,—CH(CH₃)—, —CH₂—CH₂—CH₂—, —CH(CH₃)—CH₂—, —CH(CH₂CH₃)—, —CH₂—(CH₂)₂—CH₂—,—CH(CH₃)—CH₂—CH₂—, —CH₂—CH(CH₃)—CH₂—, —CH(CH₃)—CH(CH₃)—,—CH(CH₂CH₃)—CH₂—, —C(CH₃)₂—CH₂—, —CH(CH₂CH₂CH₃)—, —C(CH₃)(CH₂CH₃)—,—CH₂—(CH₂)₃—CH₂—, —CH(CH₃)—CH₂—CH₂—CH₂—, —CH₂—CH(CH₃)—CH₂—CH₂—,—CH(CH₃)—CH₂—CH(CH₃)—, —CH(CH₃)—CH(CH₃)—CH₂—, —C(CH₃)₂—CH₂—CH₂—,—CH₂—C(CH₃)₂—CH₂—, —CH(CH₂CH₃)—CH₂—CH₂—, —CH₂—CH(CH₂CH₃)—CH₂—,—O(CH₃)₂—CH(CH₃)—, —CH(CH₂CH₃)—CH(CH₃)—, —C(CH₃)(CH₂CH₃)—CH₂—,—CH(CH₂CH₂CH₃)—CH₂—, —C(CH₂CH₂CH₃)—CH₂—, —CH(CH₂CH₂CH₂CH₃)—,—C(CH₃)(CH₂CH₂CH₃)—, —C(CH₂CH₃)₂— and —CH₂—(CH₂)₄—CH₂—. Preferred C₂₋₈alkenylene groups are selected from the group consisting of —CH═CH—,—CH═CH—CH₂—, —C(CH₃)═CH₂—, —CH═CH—CH₂—CH₂—, —CH₂—CH═CH—CH₂—,—CH═CH—CH═CH—, —C(CH₃)═CH—CH₂—, —CH═C(CH₃)—CH₂—, —C(CH₃)═C(CH₃)—,—C(CH₂CH₃)═CH—, —CH═CH—CH₂—CH₂—CH₂—, —CH₂—CH═CH₂—CH₂—CH₂—,—CH═CH═CH—CH₂—CH₂— and —CH═CH₂—CH—CH═CH₂—. Preferred C₂₋₈ alkynylenegroups are selected from the group consisting of —C≡C—, —C≡C—CH₂—,—C≡C—CH₂—CH₂—, —C≡C—CH(CH₃)—, —CH₂—C≡C—CH₂—, —C≡C—C═C—, —C≡C—C(CH₃)₂—,—C≡C—CH₂—CH₂—CH₂—, —CH₂—C≡C—CH₂—CH₂—, —C≡C—C≡C—CH₂— and —C≡C—CH₂—C≡C.

In relation to “aliphatic residue” and “aliphatic group” the term “mono-or polysubstituted” refers in the sense of this invention, with respectto the corresponding residues or groups, to the single substitution ormultiple substitution, e.g. disubstitution, trisubstitution andtetrasubstitution, of one or more hydrogen atoms each independently ofone another by at least one substituent selected from the groupconsisting of F, Cl, Br, I, NO₂, NH₂, an NH(C₁₋₄ aliphatic residue), anN(C₁₋₄ aliphatic residue)₂, a NH—C(═O)—C₁₋₄ aliphatic residue, aNH—S(═O)₂—C₁₋₄ aliphatic residue, ═O, OH, OCF₃, a O—C₁₋₄-aliphaticresidue, a O—C(═O)—C₁₋₄-aliphatic residue, SH, SCF₃, a S—C₁₋₄-aliphaticresidue, S(═O)₂OH, a S(═O)₂—C₁₋₄-aliphatic residue, aS(═O)₂—O—C₁₋₄-aliphatic residue, a S(═O)₂—NH—C₁₋₄-aliphatic residue, CN,CF₃, CHO, COOH, a C₁₋₄-aliphatic residue, a C(═O)—C₁₋₄-aliphaticresidue, a C(═O)—O—C₁₋₄-aliphatic residue, a C₃₋₆-cycloaliphaticresidue, a 3 to 6 membered heterocycloaliphatic residue, C(═O)—NH₂, aC(═O)—NH(C₁₋₄ aliphatic residue), and a C(═O)—N(C₁₋₄ aliphaticresidue)₂. The term “polysubstituted” with respect to polysubstitutedresidues and groups includes the polysubstitution of these residues andgroups either on different or on the same atoms, for exampletrisubstituted on the same carbon atom, as in the case of CF₃ or CH₂CF₃,or at various points, as in the case of CH(OH)—CH═CH—CHCl₂. Asubstituent can if appropriate for its part in turn be mono- orpolysubstituted. The multiple substitution can be carried out using thesame or using different substituents.

In relation to “cycloaliphatic residue” and “heterocycloaliphaticresidue” the term “mono- or polysubstituted” refers in the sense of thisinvention, with respect to the corresponding residues, to the singlesubstitution or multiple substitution, e.g. disubstitution,trisubstitution and tetrasubstitution, of one or more hydrogen atomseach independently of one another by at least one substituent selectedfrom the group consisting of F, Cl, Br, I, NO₂, NH₂, an NH(C₁₋₄aliphatic residue), an N(C₁₋₄ aliphatic residue)₂, a NH—C(═O)—C₁₋₄aliphatic residue, a NH—S(═O)₂—C₁₋₄ aliphatic residue, ═O, OH, OCF₃, aO—C₁₋₄-aliphatic residue, a O—C(═O)—C₁₋₄-aliphatic residue, SH, SCF₃, aS—C₁₋₄-aliphatic residue, S(═O)₂OH, a S(═O)₂—C₁₋₄-aliphatic residue, aS(═O)₂—O—C₁₋₄-aliphatic residue, a S(═O)₂—NH—C₁₋₄-aliphatic residue, CN,CF₃, CHO, COOH, a C₁₋₄-aliphatic residue, a C(═O)—C₁₋₄-aliphaticresidue, a C(═O)—O—C₁₋₄-aliphatic residue, a C₃₋₆-cycloaliphaticresidue, a 3 to 6 membered heterocycloaliphatic residue, C(═O)—NH₂, aC(═O)—NH(C₁₋₄ aliphatic residue), and a C(═O)—N(C₁₋₄ aliphaticresidue)₂. The term “polysubstituted” with respect to polysubstitutedresidues and groups includes the polysubstitution of these residues andgroups either on different or on the same atoms, for exampledisubstituted on the same carbon atom, as in the case of1,1-difluorocyclohexyl, or at various points, as in the case of1-chloro-3-fluorocyclohexyl. A substituent can if appropriate for itspart in turn be mono- or polysubstituted. The multiple substitution canbe carried out using the same or using different substituents.

Preferred substituents of “aliphatic residue” and “aliphatic group” areselected from the group consisting of F, Cl, Br, I, NO₂, NH₂, an NH(C₁₋₄aliphatic residue), an N(C₁₋₄ aliphatic residue)₂, ═O, OH, OCF₃, aO—C₁₋₄-aliphatic residue, SH, SCF₃, a S—C₁₋₄-aliphatic residue, aS(═O)₂—C₁₋₄-aliphatic residue, a S(═O)₂—NH—C₁₋₄-aliphatic residue, CN,CF₃, a C₁₋₄-aliphatic residue, a C(═O)—C₁₋₄-aliphatic residue, aC(═O)—O—C₁₋₄-aliphatic residue, CONH₂, a C(═O)—NH(C₁₋₄ aliphaticresidue), and a C(═O)—N(C₁₋₄ aliphatic residue)₂.

Preferred substituents of “cycloaliphatic residue” and“heterocycloaliphatic residue” are selected from the group consisting ofF, Cl, Br, I, NO₂, NH₂, an NH(C₁₋₄ aliphatic residue), an N(C₁₋₄aliphatic residue)₂, ═O, OH, OCF₃, a O—C₁₋₄-aliphatic residue, SH, SCF₃,a S—C₁₋₄-aliphatic residue, a S(═O)₂—C₁₋₄-aliphatic residue, aS(═O)₂—NH—C₁₋₄-aliphatic residue, CN, CF₃, a C₁₋₄-aliphatic residue, aC(═O)—C₁₋₄-aliphatic residue, a C(═O)—O—C₁₋₄-aliphatic residue, CONH₂, aC(═O)—NH(C₁₋₄ aliphatic residue), and a C(═O)—N(C₁₋₄ aliphaticresidue)₂.

In relation to “aryl” and “heteroaryl” the term “mono- orpolysubstituted” refers in the sense of this invention to the singlesubstitution or multiple substitution, e.g. disubstitution,trisubstitution and tetrasubstitution, of one or more hydrogen atomseach independently of one another by at least one substituent selectedfrom the group consisting of F, Cl, Br, I, NO₂, NH₂,

an NH(C₁₋₄ aliphatic residue), an N(C₁₋₄ aliphatic residue)₂, anNH—C(═O)—C₁₋₄ aliphatic residue, an NH—S(═O)₂—C₁₋₄ aliphatic residue,OH, OCF₃, a O—C₁₋₄-aliphatic residue, a O—C(═O)—C₁₋₄-aliphatic residue,SH, SCF₃, a S—C₁₋₄-aliphatic residue, S(═O)₂OH, a S(═O)₂—C₁₋₄-aliphaticresidue, a S(═O)₂—O—C₁₋₄-aliphatic residue, a S(═O)₂—NH—C₁₋₄-aliphaticresidue, CN, CF₃, C(═O)H, C(═O)OH, a C₁₋₄-aliphatic residue, aC(═O)—C₁₋₄-aliphatic residue, a C(═O)—O—C₁₋₄-aliphatic residue, aC₃₋₆-cycloaliphatic residue, a 3 to 6 membered heterocycloaliphaticresidue, benzyl, aryl, heteroaryl, C(═O)—NH₂, a C(═O)—NH(C₁₋₄ aliphaticresidue), and a C(═O)—N(C₁₋₄ aliphatic residue)₂ on one or ifappropriate different atoms, wherein a substituent can if appropriatefor its part in turn be mono- or polysubstituted. The multiplesubstitution is carried out employing the same or using differentsubstituents.

Preferred substituents of “aryl” and “heteroaryl” are selected from thegroup consisting of F, Cl, Br, I, NO₂, NH₂,

an NH(C₁₋₄ aliphatic residue), an N(C₁₋₄ aliphatic residue)₂, anNH—C(═O)—C₁₋₄ aliphatic residue, an NH—S(═O)₂—C₁₋₄ aliphatic residue,OH, OCF₃, a O—C₁₋₄-aliphatic residue, SH, SCF₃, a S—C₁₋₄-aliphaticresidue, S(═O)₂OH, a S(═O)₂—C₁₋₄-aliphatic residue, aS(═O)₂—NH—C₁₋₄-aliphatic residue, CN, CF₃, a C₁₋₄-aliphatic residue, aC(═O)—C₁₋₄-aliphatic residue, a C(═O)—O—C₁₋₄-aliphatic residue, aC₃₋₆-cycloaliphatic residue, a 3 to 6 membered heterocycloaliphaticresidue, CONH₂, a C(═O)—NH(C₁₋₄ aliphatic residue), a C(═O)—N(C₁₋₄aliphatic residue)₂, aryl, preferably phenyl, or benzyl, in each caseunsubstituted or mono- or polysubstituted with at least one substituentselected from the group consisting of F, Cl, Br, I, CN, CF₃, CH₃, C₂H₅,iso-propyl, tert.-butyl, C(═O)—OH, C(═O)—CH₃, C(═O)—C₂H₅, C(═O)—O—CH₃and C(═O)—O—C₂H₅, O—CH₃, OCF₃, O—CH₂—OH, O—CH₂—O—CH₃, SH, S—CH₃, SCF₃,NO₂, NH₂, N(CH₃)₂, N(CH₃)(C₂H₅) and N(C₂H₅)₂, heteroaryl, preferablypyridyl, thienyl, furyl, thiazolyl or oxazolyl, in each caseunsubstituted or mono- or polysubstituted with at least one substituentselected from the group consisting of F, Cl, Br, I, CN, CF₃, CH₃, C₂H₅,iso-propyl, tert.-butyl, C(═O)—OH, C(═O)—CH₃, C(═O)—C₂H₅, C(═O)—O—CH₃and C(═O)—O—C₂H₅, O—CH₃, OCF₃, O—CH₂—OH, O—CH₂—O—CH₃, SH, S—CH₃, SCF₃,NO₂, NH₂, N(CH₃)₂, N(CH₃)(C₂H₅) and N(C₂H₅)₂.

The compounds according to the invention are defined by substituents,for example by R¹, R² and R³ (1^(st) generation substituents) which arefor their part if appropriate substituted (2^(nd) generationsubstituents). Depending on the definition, these substituents of thesubstituents can for their part be resubstituted (3^(rd) generationsubstituents). If, for example, R¹=a C₁₋₁₀ aliphatic residue (1^(st)generation substituent), then the C₁₋₄ aliphatic residue can for itspart be substituted, for example with a NH—C₁₋₄ aliphatic residue(2^(nd) generation substituent). This produces the functional groupR¹═(C₁₋₁₀ aliphatic residue-NH—C₁₋₄ aliphatic residue). The NH—C₁₋₄aliphatic residue can then for its part be resubstituted, for examplewith Cl (3^(rd) generation substituent). Overall, this produces thefunctional group R¹═C₁₋₁₀ aliphatic residue-NH—C₁₋₄ aliphatic residue,wherein the C₁₋₄ aliphatic residue of the NH—C₁₋₄ aliphatic residue issubstituted by Cl.

However, in a preferred embodiment, the 3^(rd) generation substituentsmay not be resubstituted, i.e. there are then no 4^(th) generationsubstituents.

In another preferred embodiment, the 2^(nd) generation substituents maynot be resubstituted, i.e. there are then not even any 3^(rd) generationsubstituents. In other words, in this embodiment, in the case of generalformula (I), for example, the functional groups for R¹ to R⁷ can each ifappropriate be substituted; however, the respective substituents maythen for their part not be resubstituted.

In some cases, the compounds according to the invention are defined bysubstituents which are or carry an aryl or heteroaryl residue,respectively unsubstituted or mono- or polysubstituted, or which formtogether with the carbon atom(s) or heteroatom(s) connecting them, asthe ring member or as the ring members, a ring, for example an aryl orheteroaryl, in each case unsubstituted or mono- or polysubstituted. Boththese aryl or heteroaryl residues and the (hetero)aromatic ring systemsformed in this way can if appropriate be condensed with acycloaliphatic, preferably a C₃₋₆ cycloaliphatic residue, orheterocycloaliphatic residue, preferably a 3 to 6 memberedheterocycloaliphatic residue, or with aryl or heteroaryl, e.g. with aC₃₋₆ cycloaliphatic residue such as cyclopentyl, or a 3 to 6 memberedheterocycloaliphatic residue such as morpholinyl, or an aryl such asphenyl, or a heteroaryl such as pyridyl, wherein the cycloaliphatic orheterocycloaliphatic residues, aryl or heteroaryl residues condensed inthis way can for their part be respectively unsubstituted or mono- orpolysubstituted.

In some cases, the compounds according to the invention are defined bysubstituents which are or carry a cycloaliphatic residue or aheterocycloaliphatic residue, respectively, in each case unsubstitutedor mono- or polysubstituted, or which form together with the carbonatom(s) or heteroatom(s) connecting them, as the ring member or as thering members, a ring, for example a cycloaliphatic or aheterocycloaliphatic ring system. Both these cycloaliphatic orheterocycloaliphatic ring systems and the (hetero)cycloaliphatic ringsystems formed in this manner can if appropriate be condensed with arylor heteroaryl or with a cycloaliphatic residue, preferably a C₃₋₆cycloaliphatic residue, or a heterocycloaliphatic residue, preferably a3 to 6 membered heterocycloaliphatic residue, e.g. with an aryl such asphenyl, or a heteroaryl such as pyridyl, or a cycloaliphatic residuesuch as cyclohexyl, or a heterocycloaliphatic residue such asmorpholinyl, wherein the aryl or heteroaryl residues or cycloaliphaticor heterocycloaliphatic residues condensed in this way can for theirpart be respectively unsubstituted or mono- or polysubstituted.

Within the scope of the present invention, the symbol

used in the formulae denotes a link of a corresponding residue to therespective superordinate general structure.

If a residue occurs multiply within a molecule, then this residue canhave respectively different meanings for various substituents: if, forexample, both R² and R³ denote a 3 to 6 membered heterocycloaliphaticresidue, then the 3 to 6 membered heterocycloaliphatic residue can e.g.represent morpholinyl for R² and can represent piperazinyl for R³.

The term “salts of physiologically acceptable acids” refers in the senseof this invention to salts of the respective active ingredient withinorganic or organic acids which are physiologically acceptable—inparticular when used in human beings and/or other mammals. Hydrochlorideis particularly preferred. Examples of physiologically acceptable acidsare: hydrochloric acid, hydrobromic acid, sulphuric acid,methanesulphonic acid, p-toluenesulphonic acid, carbonic acid, formicacid, acetic acid, oxalic acid, succinic acid, tartaric acid, mandelicacid, fumaric acid, maleic acid, lactic acid, citric acid, glutamicacid, saccharic acid, monomethylsebacic acid, 5-oxoproline,hexane-1-sulphonic acid, nicotinic acid, 2, 3 or 4-aminobenzoic acid,2,4,6-trimethylbenzoic acid, α-lipoic acid, acetyl glycine, hippuricacid, phosphoric acid, aspartic acid. Citric acid and hydrochloric acidare particularly preferred.

The term “salts of physiologically acceptable bases” refers in the senseof this invention to salts of the respective compound according to theinvention—as an anion, e.g. upon deprotonation of a suitable functionalgroup—with at least one cation or base—preferably with at least oneinorganic cation—which are physiologically acceptable—in particular whenused in human beings and/or other mammals. Particularly preferred arethe salts of the alkali and alkaline earth metals, in particular (mono-)or (di)sodium, (mono-) or (di)potassium, magnesium or calcium salts, butalso ammonium salts [NH_(x)R_(4-x)]⁺, in which x=0, 1, 2, 3 or 4 and Rrepresents a branched or unbranched C₁ aliphatic residue.

Preferred embodiments of the compound according to general formula (I)have general formulae (Ia), (Ib), (Ic) or (Id):

Another preferred embodiment of present invention is a compoundaccording to general formula (I), wherein

-   R¹ denotes a C₁₋₁₀-aliphatic residue, preferably a C₁₋₈-aliphatic    residue, unsubstituted or mono- or polysubstituted with at least one    substituent selected from the group consisting of F, Cl, Br, I, NO₂,    NH₂, an NH(C₁₋₄ aliphatic residue), an N(C₁₋₄ aliphatic residue)₂,    OH, ═O, an O—C₁₋₄-aliphatic residue, OCF₃, SH, SCF₃, a    S—C₁₋₄-aliphatic residue, CF₃, CN, a C₁₋₄-aliphatic residue and    C(═O)—OH,    -   wherein the C₁₋₄-aliphatic residue in each case may be        unsubstituted or mono- or polysubstituted with at least one        substituent selected from the group consisting of F, Cl, Br, I,        OH, OCF₃, CF₃ and an unsubstituted O—C₁₋₄-aliphatic residue,    -   or denotes a C₃₋₁₀-cycloaliphatic residue or a 3 to 10 membered        heterocycloaliphatic residue, in each case unsubstituted or        mono- or polysubstituted with at least one substituent selected        from the group consisting of F, Cl, Br, I, NO₂, NH₂, an NH(C₁₋₄        aliphatic residue), an N(C₁₋₄ aliphatic residue)₂, OH, ═O, an        O—C₁₋₄ aliphatic residue, OCF₃, SH, SCF₃, a S—C₁₋₄ aliphatic        residue, CF₃, CN, a C₁₋₄-aliphatic residue, C(═O)—OH, a C₃₋₆        cycloaliphatic residue, and a 3 to 6 membered        heterocycloaliphatic residue,        -   wherein the C₁₋₄-aliphatic residue in each case may be            unsubstituted or mono- or polysubstituted with at least one            substituent selected from the group consisting of F, Cl, Br,            I, OH, OCF₃, CF₃ and an unsubstituted O—C₁₋₄-aliphatic            residue, and        -   wherein the C₃₋₆ cycloaliphatic residue and the 3 to 6            membered heterocycloaliphatic residue may in each case may            be unsubstituted or mono- or polysubstituted with at least            one substituent selected from the group consisting of F, Cl,            Br, I, NO₂, NH₂, an NH(C₁₋₄ aliphatic residue), an N(C₁₋₄            aliphatic residue)₂, OH, ═O, an O—C₁₋₄ aliphatic residue,            OCF₃, SH, SCF₃, a S—C₁₋₄ aliphatic residue, CF₃, CN, a            C₁₋₄-aliphatic residue and C(═O)—OH,    -   and wherein the C₃₋₁₀-cycloaliphatic residue or the 3 to 10        membered heterocycloaliphatic residue may in each case        optionally bridged via a C₁₋₈ aliphatic group, preferably a C₁₋₄        aliphatic group, which in turn may be unsubstituted or mono- or        polysubstituted with at least one substituent selected from the        group consisting of F, Cl, Br, I, NO₂, NH₂, an NH(C₁₋₄ aliphatic        residue), an N(C₁₋₄ aliphatic residue)₂, OH, ═O, an O—C₁₋₄        aliphatic residue, OCF₃, SH, SCF₃, a S—C₁₋₄ aliphatic residue,        CF₃, CN, a C₁₋₄-aliphatic residue and C(═O)—OH,    -   or denotes an aryl or heteroaryl, in each case unsubstituted or        mono- or polysubstituted with at least one substituent selected        from the group consisting of F, Cl, Br, I, NO₂, NH₂, an NH(C₁₋₄        aliphatic residue), an N(C₁₋₄ aliphatic residue)₂, OH, an O—C₁₋₄        aliphatic residue, OCF₃, SH, SCF₃, a S—C₁₋₄ aliphatic residue,        CF₃, CN, a C₁₋₄-aliphatic residue, C(═O)—OH, C(═O)—CH₃,        C(═O)—C₂H₅, C(═O)—O—CH₃ and C(═O)—O—C₂H₅, a C₃₋₆ cycloaliphatic        residue, a 3 to 6 membered heterocycloaliphatic residue,

-   -    benzyl, phenyl, thienyl, pyridyl, furyl, thiazolyl and        oxazolyl,        -   wherein the C₁₋₄-aliphatic residue in each case may be            unsubstituted or mono- or polysubstituted with at least one            substituent selected from the group consisting of F, Cl, Br,            I, OH, OCF₃, CF₃ and an unsubstituted O—C₁₋₄-aliphatic            residue, and        -   wherein benzyl, phenyl, thienyl, pyridyl, furyl, thiazolyl            and oxazolyl may in each case may be unsubstituted or mono-            or polysubstituted with at least one substituent selected            from the group consisting of F, Cl, Br, I, NO₂, NH₂, an            NH(C₁₋₄ aliphatic residue), an N(C₁₋₄ aliphatic residue)₂,            OH, an O—C₁₋₄ aliphatic residue, OCF₃, O—CH₂—OH,            O—CH₂—O—CH₃, SH, SCF₃, a S—C₁₋₄ aliphatic residue, CF₃, CN,            a C₁₋₄-aliphatic residue, C(═O)—OH, C(═O)—CH₃, C(═O)—C₂H₅,            C(═O)—O—CH₃ and C(═O)—O—C₂H₅, and        -   wherein the C₃₋₆ cycloaliphatic residue and the 3 to 6            membered heterocycloaliphatic residue may in each case may            be unsubstituted or mono- or polysubstituted with at least            one substituent selected from the group consisting of F, Cl,            Br, I, NO₂, NH₂, an NH(C₁₋₄ aliphatic residue), an N(C₁₋₄            aliphatic residue)₂, OH, ═O, an O—C₁₋₄ aliphatic residue,            OCF₃, SH, SCF₃, a S—C₁₋₄ aliphatic residue, CF₃, CN, a            C₁₋₄-aliphatic residue and C(═O)—OH,    -   and wherein the aryl or the heteroaryl residue may in each case        be optionally bridged via a C₁₋₈ aliphatic group, preferably a        C₁₋₄ aliphatic group, which in turn may be unsubstituted or        mono- or polysubstituted with at least one substituent selected        from the group consisting of F, Cl, Br, I, NO₂, NH₂, an NH(C₁₋₄        aliphatic residue), an N(C₁₋₄ aliphatic residue)₂, OH, ═O, an        O—C₁₋₄ aliphatic residue, OCF₃, SH, SCF₃, a S—C₁₋₄ aliphatic        residue, CF₃, CN and C(═O)—OH,

-   R² represents H; F; Cl; Br; I; CN; CF₃; NO₂; OCF₃; SCF₃; a    C₁₋₄-aliphatic residue, a S—C₁₋₄-aliphatic residue, a    O—C₁₋₄-aliphatic residue, wherein the C₁₋₄ aliphatic residue may be    in each case be unsubstituted or mono- or polysubstituted; a    C₃₋₆-cycloaliphatic residue or a 3 to 6 membered    heterocycloaliphatic residue, in each case unsubstituted or mono- or    polysubstituted and in each case optionally bridged via a C₁₋₄    aliphatic group, which in turn may be unsubstituted or mono- or    polysubstituted, preferably represents H; F; Cl; Br; I; CN; CF₃;    NO₂; OCF₃; SCF₃; a C₁₋₄-aliphatic residue, a S—C₁₋₄-aliphatic    residue, a O—C₁₋₄-aliphatic residue, wherein the C₁₋₄-aliphatic    residue in each case may be unsubstituted or mono- or    polysubstituted with at least one substituent selected from the    group consisting of F, Cl, Br, I, ═O, OH, and an unsubstituted    O—C₁₋₄-aliphatic residue; a C₃₋₆-cycloaliphatic residue or a 3 to 6    membered heterocycloaliphatic residue, in each case unsubstituted or    mono- or polysubstituted with at least one substituent selected from    the group consisting of F, Cl, Br, I, ═O, OH, a C₁₋₄-aliphatic    residue and an O—C₁₋₄-aliphatic residue, wherein the C₁₋₄-aliphatic    residue in each case may be unsubstituted or mono- or    polysubstituted with at least one substituent selected from the    group consisting of F, Cl, Br, I, ═O, OH, and an unsubstituted    O—C₁₋₄-aliphatic residue, and wherein the C₃₋₆-cycloaliphatic    residue or the 3 to 6 membered heterocycloaliphatic residue may in    each case be optionally bridged via a C₁₋₄ aliphatic group, which in    turn may be unsubstituted or mono- or polysubstituted with at least    one substituent selected from the group consisting of F, Cl, Br, I,    ═O, OH, an unsubstituted C₁₋₄-aliphatic residue and an unsubstituted    O—C₁₋₄-aliphatic residue,

-   R³, R⁴, R⁵ and R⁶ each independently of one another represent H; F;    Cl; Br; I; CN; CF₃; OCF₃; SCF₃; C(═O)H; C(═O)—OH; C(═O)—NH₂;    S(═O)₂—OH; NO₂; a C₁₋₄-aliphatic residue, a C(═O)—C₁₋₄ aliphatic    residue, a C(═O)—O—C₁₋₄ aliphatic residue, a C(═O)—NH—C₁₋₄ aliphatic    residue, a C(═O)—N(C₁₋₄ aliphatic residue)₂, a O—C₁₋₄-aliphatic    residue, a O—C(═O)—C₁₋₄-aliphatic residue, a S—C₁₋₄-aliphatic    residue, a S(═O)₂—C₁₋₄-aliphatic residue, a NH(C₁₋₄ aliphatic    residue), a N(C₁₋₄ aliphatic residue)₂, a NH—C(═O)—C₁₋₄ aliphatic    residue, and a NH—S(═O)₂—C₁₋₄-aliphatic residue, wherein the    C₁₋₄-aliphatic residue in each case may be unsubstituted or mono- or    polysubstituted with at least one substituent selected from the    group consisting of F, Cl, Br, I, ═O, OH, and a O—C₁₋₄-aliphatic    residue; a C₃₋₆-cycloaliphatic residue or a 3 to 6 membered    heterocycloaliphatic residue, in each case unsubstituted or mono- or    polysubstituted with at least one substituent selected from the    group consisting of F, Cl, Br, I, ═O, OH, a C₁₋₄-aliphatic residue    and a O—C₁₋₄-aliphatic residue, and in each case optionally bridged    via an unsubstituted C₁₋₄ aliphatic group,    preferably on the condition that at least one of R³, R⁴, R⁵ and R⁶    is ≠H,

-   R⁷ denotes a C₁₋₁₀-aliphatic residue, preferably a C₁₋₈-aliphatic    residue, unsubstituted or mono- or polysubstituted with at least one    substituent selected from the group consisting of F, Cl, Br, I, NO₂,    NH₂, an NH(C₁₋₄ aliphatic residue), an N(C₁₋₄ aliphatic residue)₂,    OH, ═O, an O—C₁₋₄-aliphatic residue, OCF₃, SH, SCF₃, a    S—C₁₋₄-aliphatic residue, CF₃, CN, a C₁₋₄-aliphatic residue and    C(═O)—OH,    -   wherein the C₁₋₄-aliphatic residue in each case may be        unsubstituted or mono- or polysubstituted with at least one        substituent selected from the group consisting of F, Cl, Br, I,        OH, OCF₃, CF₃ and an unsubstituted O—C₁₋₄-aliphatic residue,    -   or denotes a C₃₋₄₀-cycloaliphatic residue or a 3 to 10 membered        heterocycloaliphatic residue, in each case unsubstituted or        mono- or polysubstituted with at least one substituent selected        from the group consisting of F, Cl, Br, I, NO₂, NH₂, an NH(C₁₋₄        aliphatic residue), an N(C₁₋₄ aliphatic residue)₂, OH, ═O, an        O—C₁₋₄ aliphatic residue, OCF₃, SH, SCF₃, a S—C₁₋₄ aliphatic        residue, CF₃, CN, a C₁₋₄-aliphatic residue, C(═O)—OH, a C₃₋₆        cycloaliphatic residue, and a 3 to 6 membered        heterocycloaliphatic residue,        -   wherein the C₁₋₄-aliphatic residue in each case may be            unsubstituted or mono- or polysubstituted with at least one            substituent selected from the group consisting of F, Cl, Br,            I, OH, OCF₃, CF₃ and an unsubstituted O—C₁₋₄-aliphatic            residue, and        -   wherein the C₃₋₆ cycloaliphatic residue and the 3 to 6            membered heterocycloaliphatic residue may in each case may            be unsubstituted or mono- or polysubstituted with at least            one substituent selected from the group consisting of F, Cl,            Br, I, NO₂, NH₂, an NH(C₁₋₄ aliphatic residue), an N(C₁₋₄            aliphatic residue)₂, OH, ═O, an O—C₁₋₄ aliphatic residue,            OCF₃, SH, SCF₃, a S—C₁₋₄ aliphatic residue, CF₃, CN, a            C₁₋₄-aliphatic residue and C(═O)—OH,    -   and wherein the C₃₋₁₀-cycloaliphatic residue or the 3 to 10        membered heterocycloaliphatic residue may in each case        optionally bridged via a C₁₋₈ aliphatic group, preferably a C₁₋₄        aliphatic group, which in turn may be unsubstituted or mono- or        polysubstituted with at least one substituent selected from the        group consisting of F, Cl, Br, I, NO₂, NH₂, an NH(C₁₋₄ aliphatic        residue), an N(C₁₋₄ aliphatic residue)₂, OH, ═O, an O—C₁₋₄        aliphatic residue, OCF₃, SH, SCF₃, a S—C₁₋₄ aliphatic residue,        CF₃, CN, a C₁₋₄-aliphatic residue and C(═O)—OH,    -   on the condition that if R⁷ denotes a 3 to 10 membered        heterocycloaliphatic residue, the 3 to 10 membered        heterocycloaliphatic residue is linked via a carbon atom.

In a preferred embodiment of the compound according to general formula(I), the residue

-   R¹ denotes a C₁₋₁₀-aliphatic residue, preferably a C₁₋₈-aliphatic    residue, unsubstituted or mono- or polysubstituted with at least one    substituent selected from the group consisting of F, Cl, Br, I, NO₂,    NH₂, an NH(C₁₋₄ aliphatic residue), an N(C₁₋₄ aliphatic residue)₂,    OH, ═O, an O—C₁₋₄-aliphatic residue, OCF₃, SH, SCF₃, a    S—C₁₋₄-aliphatic residue, CF₃, CN, a C₁₋₄-aliphatic residue and    C(═O)—OH,    -   wherein the C₁₋₄-aliphatic residue in each case may be        unsubstituted or mono- or polysubstituted with at least one        substituent selected from the group consisting of F, Cl, Br, I,        OH, OCF₃, CF₃ and an unsubstituted O—C₁₋₄-aliphatic residue,    -   or denotes a C₃₋₁₀-cycloaliphatic residue or a 3 to 10 membered        heterocycloaliphatic residue, in each case unsubstituted or        mono- or polysubstituted with at least one substituent selected        from the group consisting of F, Cl, Br, I, NO₂, NH₂, an NH(C₁₋₄        aliphatic residue), an N(C₁₋₄ aliphatic residue)₂, OH, ═O, an        O—C₁₋₄ aliphatic residue, OCF₃, SH, SCF₃, a S—C₁₋₄ aliphatic        residue, CF₃, CN, a C₁₋₄-aliphatic residue, C(═O)—OH, a C₃₋₆        cycloaliphatic residue, and a 3 to 6 membered        heterocycloaliphatic residue,        -   wherein the C₁₋₄-aliphatic residue in each case may be            unsubstituted or mono- or polysubstituted with at least one            substituent selected from the group consisting of F, Cl, Br,            I, OH, OCF₃, CF₃ and an unsubstituted O—C₁₋₄-aliphatic            residue, and        -   wherein the C₃₋₆ cycloaliphatic residue and the 3 to 6            membered heterocycloaliphatic residue may in each case may            be unsubstituted or mono- or polysubstituted with at least            one substituent selected from the group consisting of F, Cl,            Br, I, NO₂, NH₂, an NH(C₁₋₄ aliphatic residue), an N(C₁₋₄            aliphatic residue)₂, OH, ═O, an O—C₁₋₄ aliphatic residue,            OCF₃, SH, SCF₃, a S—C₁₋₄ aliphatic residue, CF₃, CN, a            C₁₋₄-aliphatic residue and C(═O)—OH,    -   and wherein the C₃₋₁₀-cycloaliphatic residue or the 3 to 10        membered heterocycloaliphatic residue may in each case        optionally bridged via a C₁₋₈ aliphatic group, preferably a C₁₋₄        aliphatic group, which in turn may be unsubstituted or mono- or        polysubstituted with at least one substituent selected from the        group consisting of F, Cl, Br, I, NO₂, NH₂, an NH(C₁₋₄ aliphatic        residue), an N(C₁₋₄ aliphatic residue)₂, OH, ═O, an O—C₁₋₄        aliphatic residue, OCF₃, SH, SCF₃, a S—C₁₋₄ aliphatic residue,        CF₃, CN, a C₁₋₄-aliphatic residue and C(═O)—OH,    -   or denotes an aryl or heteroaryl, in each case unsubstituted or        mono- or polysubstituted with at least one substituent selected        from the group consisting of F, Cl, Br, I, NO₂, NH₂, an NH(C₁₋₄        aliphatic residue), an N(C₁₋₄ aliphatic residue)₂, OH, an O—C₁₋₄        aliphatic residue, OCF₃, SH, SCF₃, a S—C₁₋₄ aliphatic residue,        CF₃, CN, a C₁₋₄-aliphatic residue, C(═O)—OH, C(═O)—CH₃,        C(═O)—C₂H₅, C(═O)—O—CH₃ and C(═O)—O—C₂H₅, a C₃₋₆ cycloaliphatic        residue, a 3 to 6 membered heterocycloaliphatic residue,

-   -    benzyl, phenyl, thienyl, pyridyl, furyl, thiazolyl and        oxazolyl,        -   wherein the C₁₋₄-aliphatic residue in each case may be            unsubstituted or mono- or polysubstituted with at least one            substituent selected from the group consisting of F, Cl, Br,            I, OH, OCF₃, CF₃ and an unsubstituted O—C₁₋₄-aliphatic            residue, and        -   wherein benzyl, phenyl, thienyl, pyridyl, furyl, thiazolyl            and oxazolyl may in each case may be unsubstituted or mono-            or polysubstituted with at least one substituent selected            from the group consisting of F, Cl, Br, I, NO₂, NH₂, an            NH(C₁₋₄ aliphatic residue), an N(C₁₋₄ aliphatic residue)₂,            OH, an O—C₁₋₄ aliphatic residue, OCF₃, O—CH₂—OH,            O—CH₂—O—CH₃, SH, SCF₃, a S—C₁₋₄ aliphatic residue, CF₃, CN,            a C₁₋₄-aliphatic residue, C(═O)—OH, C(═O)—CH₃, C(═O)—C₂H₅,            C(═O)—O—CH₃ and C(═O)—O—C₂H₅, and        -   wherein the C₃₋₆ cycloaliphatic residue and the 3 to 6            membered heterocycloaliphatic residue may in each case may            be unsubstituted or mono- or polysubstituted with at least            one substituent selected from the group consisting of F, Cl,            Br, I, NO₂, NH₂, an NH(C₁₋₄ aliphatic residue), an N(C₁₋₄            aliphatic residue)₂, OH, ═O, an O—C₁₋₄ aliphatic residue,            OCF₃, SH, SCF₃, a S—C₁₋₄ aliphatic residue, CF₃, CN, a            C₁₋₄-aliphatic residue and C(═O)—OH,    -   and wherein the aryl or the heteroaryl residue may in each case        be optionally bridged via a C₁₋₈ aliphatic group, preferably a        C₁₋₄ aliphatic group, which in turn may be unsubstituted or        mono- or polysubstituted with at least one substituent selected        from the group consisting of F, Cl, Br, I, NO₂, NH₂, an NH(C₁₋₄        aliphatic residue), an N(C₁₋₄ aliphatic residue)₂, OH, ═O, an        O—C₁₋₄ aliphatic residue, OCF₃, SH, SCF₃, a S—C₁₋₄ aliphatic        residue, CF₃, CN and C(═O)—OH.        In a further preferred embodiment of the compound according to        general formula (I), the residue

-   R¹ represents the partial structure (T1)

-   -   wherein    -   m denotes 0, 1, 2, 3 or 4, preferably denotes 0, 1, or 2,    -   R^(8a) and R^(8b) each independently of one another represent H,        F, Cl, Br, I, NO₂, NH₂, a NH(C₁₋₄ aliphatic residue), an N(C₁₋₄        aliphatic residue)₂, OH, an O—C₁₋₄ aliphatic residue, OCF₃, SH,        SCF₃, a S—C₁₋₄ aliphatic residue, CF₃, CN, a C₁₋₄ aliphatic        residue or C(═O)—OH, or together denote ═O,        -   preferably each independently of one another represent H, F,            Cl, Br, I, NH₂, a NH(C₁₋₄ aliphatic residue), a N(C₁₋₄            aliphatic residue)₂, OH, O—C₁₋₄ aliphatic residue or a C₁₋₄            aliphatic residue,        -   more preferably each independently of one another represent            H, F, Cl, Br, I, an O—C₁₋₄ aliphatic residue or a C₁₋₄            aliphatic residue,        -   even more preferably each independently of one another            represent H, F, an O—C₁₋₄ aliphatic residue or a C₁₋₄            aliphatic residue, and    -   R^(8c) denotes a C₁₋₄ aliphatic residue, unsubstituted or mono-        or polysubstituted with at least one substituent selected from        the group consisting of F, Cl, Br, I, NO₂, NH₂, an NH(C₁₋₄        aliphatic residue), an N(C₁₋₄ aliphatic residue)₂, OH, ═O, an        O—C₁₋₄ aliphatic residue, OCF₃, SH, SCF₃, a S—C₁₋₄ aliphatic        residue, CF₃, CN, a C₁₋₄-aliphatic residue and C(═O)—OH,        -   or denotes a C₃₋₁₀-cycloaliphatic residue or a 3 to 10            membered heterocycloaliphatic residue, preferably when m is            ≠0, in each case unsubstituted or mono- or polysubstituted            with at least one substituent selected from the group            consisting of F, Cl, Br, I, NO₂, NH₂, an NH(C₁₋₄ aliphatic            residue), an N(C₁₋₄ aliphatic residue)₂, OH, ═O, an O—C₁₋₄            aliphatic residue, OCF₃, SH, SCF₃, a S—C₁₋₄ aliphatic            residue, CF₃, CN, a C₁₋₄-aliphatic residue, C(═O)—OH, a C₃₋₆            cycloaliphatic residue and a 3 to 6 membered            heterocycloaliphatic residue,            -   wherein the C₁₋₄-aliphatic residue in each case may be                unsubstituted or mono- or polysubstituted with at least                one substituent selected from the group consisting of F,                Cl, Br, I, OH, OCF₃, CF₃ and an unsubstituted                O—C₁₋₄-aliphatic residue, and            -   wherein the C₃₋₆ cycloaliphatic residue and the 3 to 6                membered heterocycloaliphatic residue may in each case                may be unsubstituted or mono- or polysubstituted with at                least one substituent selected from the group consisting                of F, Cl, Br, I, NO₂, NH₂, an NH(C₁₋₄ aliphatic                residue), an N(C₁₋₄ aliphatic residue)₂, OH, ═O, an                O—C₁₋₄ aliphatic residue, OCF₃, SH, SCF₃, a S—C₁₋₄                aliphatic residue, CF₃, CN, a C₁₋₄-aliphatic residue and                C(═O)—OH,        -   or denotes—preferably when m is =0—an aryl or heteroaryl, in            each case unsubstituted or mono- or polysubstituted with at            least one substituent selected from the group consisting of            F, Cl, Br, I, NO₂, NH₂, an NH(C₁₋₄ aliphatic residue), an            N(C₁₋₄ aliphatic residue)₂, OH, an O—C₁₋₄ aliphatic residue,            OCF₃, SH, SCF₃, a S—C₁₋₄ aliphatic residue, CF₃, CN, a            C₁₋₄-aliphatic residue, C(═O)—OH, C(═O)—CH₃, C(═O)—C₂H₅,            C(═O)—O—CH₃ and C(═O)—O—C₂H₅, a C₃₋₆ cycloaliphatic residue,            a 3 to 6 membered heterocycloaliphatic residue,

-   -   -    benzyl, phenyl, thienyl, pyridyl, furyl, thiazolyl and            oxazolyl,            -   wherein the C₁₋₄-aliphatic residue in each case may be                unsubstituted or mono- or polysubstituted with at least                one substituent selected from the group consisting of F,                Cl, Br, I, OH, OCF₃, CF₃ and an unsubstituted                O—C₁₋₄-aliphatic residue, and            -   wherein benzyl, phenyl, thienyl, pyridyl, furyl,                thiazolyl and oxazolyl may in each case may be                unsubstituted or mono- or polysubstituted with at least                one substituent selected from the group consisting of F,                Cl, Br, I, NO₂, NH₂, an NH(C₁₋₄ aliphatic residue), an                N(C₁₋₄ aliphatic residue)₂, OH, an O—C₁₋₄ aliphatic                residue, OCF₃, SH, SCF₃, a S—C₁₋₄ aliphatic residue,                CF₃, CN, a C₁₋₄-aliphatic residue, C(═O)—OH, C(═O)—CH₃,                C(═O)—C₂H₅, C(═O)—O—CH₃ and C(═O)—O—C₂H₅, and            -   wherein the C₃₋₆ cycloaliphatic residue and the 3 to 6                membered heterocycloaliphatic residue may in each case                may be unsubstituted or mono- or polysubstituted with at                least one substituent selected from the group consisting                of F, Cl, Br, I, NO₂, NH₂, an NH(C₁₋₄ aliphatic                residue), an N(C₁₋₄ aliphatic residue)₂, OH, ═O, an                O—C₁₋₄ aliphatic residue, OCF₃, SH, SCF₃, a S—C₁₋₄                aliphatic residue, CF₃, CN, a C₁₋₄-aliphatic residue and                C(═O)—OH.

Preferably,

-   R¹ represents the partial structure (T1),    -   wherein    -   m denotes 0, 1, or 2,    -   R^(8a) and R^(8b) each independently of one another represent H,        F, Cl, Br, I, an O—C₁₋₄ aliphatic residue or a C₁₋₄ aliphatic        residue,        -   preferably each independently of one another represent H, F,            a O—C₁₋₂ aliphatic residue or a C₁₋₂ aliphatic residue, and    -   R^(8c) denotes a C₁₋₄ aliphatic residue, unsubstituted or mono-        or polysubstituted with at least one substituent selected from        the group consisting of F, Cl, Br, I, OH, ═O, an O—C₁₋₄        aliphatic residue, OCF₃, CF₃, a C₁₋₄-aliphatic residue and        C(═O)—OH,        -   or denotes a C₃₋₁₀-cycloaliphatic residue or a 3 to 10            membered heterocycloaliphatic residue, in each case            unsubstituted or mono- or polysubstituted with at least one            substituent selected from the group consisting of F, Cl, Br,            I, OH, ═O, an O—C₁₋₄ aliphatic residue, OCF₃, CF₃, a            C₁₋₄-aliphatic residue, C(═O)—OH, a C₃₋₆ cycloaliphatic            residue, and a 3 to 6 membered heterocycloaliphatic residue,            -   wherein the C₁₋₄-aliphatic residue in each case may be                unsubstituted or mono- or polysubstituted with at least                one substituent selected from the group consisting of F,                Cl, Br, I, OH, OCF₃, CF₃ and an unsubstituted                O—C₁₋₄-aliphatic residue, and            -   wherein the C₃₋₆ cycloaliphatic residue and the 3 to 6                membered heterocycloaliphatic residue may in each case                may be unsubstituted or mono- or polysubstituted with at                least one substituent selected from the group consisting                of F, Cl, Br, I, OH, ═O, an O—C₁₋₄ aliphatic residue,                OCF₃, CF₃, a C₁₋₄-aliphatic residue and C(═O)—OH,        -   or denotes—preferably when m is =0—an aryl or heteroaryl, in            each case unsubstituted or mono- or polysubstituted with at            least one substituent selected from the group consisting of            F, Cl, Br, I, OH, an O—C₁₋₄ aliphatic residue, OCF₃, SH,            SCF₃, a S—C₁₋₄ aliphatic residue, CF₃, CN, a C₁₋₄-aliphatic            residue, C(═O)—OH, C(═O)—CH₃, C(═O)—C₂H₅, C(═O)—O—CH₃ and            C(═O)—O—C₂H₅, a C₃₋₆ cycloaliphatic residue, a 3 to 6            membered heterocycloaliphatic residue, benzyl, phenyl,            thienyl, pyridyl, furyl, thiazolyl or oxazolyl,            -   wherein the C₁₋₄-aliphatic residue in each case may be                unsubstituted or mono- or polysubstituted with at least                one substituent selected from the group consisting of F,                Cl, Br, I, OH, OCF₃, CF₃ and an unsubstituted                O—C₁₋₄-aliphatic residue, and            -   wherein benzyl, phenyl, thienyl, pyridyl, furyl,                thiazolyl and oxazolyl may in each case may be                unsubstituted or mono- or polysubstituted, preferably                unsubstituted or mono- or disubstituted with at least                one substituent selected from the group consisting of F,                Cl, Br, I, OH, an O—C₁₋₄ aliphatic residue, OCF₃, CF₃,                CN, a C₁₋₄-aliphatic residue, C(═O)—OH, C(═O)—CH₃,                C(═O)—C₂H₅, C(═O)—O—CH₃ and C(═O)—O—C₂H₅, preferably                with at least one substituent selected from the group                consisting of F, Cl, CH₃, O—CH₃, CF₃ and OCF₃,            -   wherein the C₃₋₆ cycloaliphatic residue and the 3 to 6                membered heterocycloaliphatic residue may in each case                may be unsubstituted or mono- or polysubstituted with at                least one substituent selected from the group consisting                of F, Cl, Br, I, OH, ═O, an O—C₁₋₄ aliphatic residue,                OCF₃, CF₃ a C₁₋₄-aliphatic residue and C(═O)—OH.                More preferably,-   R¹ represents the partial structure (T1),    -   wherein    -   m denotes 0, 1, or 2,    -   R^(8a) and R^(8b) each independently of one another represent H,        F, Cl, Br, I, an O—C₁₋₄ aliphatic residue or a C₁₋₄ aliphatic        residue,    -   preferably each independently of one another represent H, F, a        O—C₁₋₂ aliphatic residue or a C₁₋₂ aliphatic residue, and    -   R^(8c) denotes a C₁₋₄ aliphatic residue, unsubstituted or mono-        or polysubstituted with at least one substituent selected from        the group consisting of F, Cl, Br, I, an O—C₁₋₄ aliphatic        residue, CF₃, and a C₁₋₄-aliphatic residue,        -   wherein the C₁₋₄-aliphatic residue in each case may be            unsubstituted or mono- or polysubstituted with at least one            substituent selected from the group consisting of F, Cl, CF₃            and an unsubstituted O—C₁₋₄-aliphatic residue,    -   or denotes a C₃₋₁₀-cycloaliphatic residue or a 3 to 10 membered        heterocycloaliphatic residue, in each case unsubstituted or        mono- or polysubstituted with at least one substituent selected        from the group consisting of F, Cl, Br, I, an O—C₁₋₄ aliphatic        residue, CF₃, and a C₁₋₄-aliphatic residue,        -   wherein the C₁₋₄-aliphatic residue in each case may be            unsubstituted or mono- or polysubstituted with at least one            substituent selected from the group consisting of F, Cl, CF₃            and an unsubstituted O—C₁₋₄-aliphatic residue,    -   or denotes—preferably when m is =0—an aryl or heteroaryl, in        each case unsubstituted or mono- or polysubstituted with at        least one substituent selected from the group consisting of F,        Cl, Br, I, OH, an O—C₁₋₄ aliphatic residue, OCF₃, CF₃, CN, a        C₁₋₄-aliphatic residue, C(═O)—CH₃, C(═O)—C₂H₅, C(═O)—O—CH₃ and        C(═O)—O—C₂H₅, a C₃₋₆ cycloaliphatic residue, a 3 to 6 membered        heterocycloaliphatic residue, benzyl, phenyl, thienyl or        pyridyl,        -   wherein benzyl, phenyl, thienyl and pyridyl, may in each            case may be unsubstituted or mono- or polysubstituted,            preferably unsubstituted or mono- or disubstituted with at            least one substituent selected from the group consisting of            F, Cl, Br, I, OH, an O—C₁₋₄ aliphatic residue, OCF₃, CF₃,            CN, a C₁₋₄-aliphatic residue, C(═O)—CH₃, C(═O)—C₂H₅,            C(═O)—O—CH₃ and C(═O)—O—C₂H₅, preferably with at least one            substituent selected from the group consisting of F, Cl,            CH₃, O—CH₃, CF₃ and OCF₃, and        -   wherein the C₃₋₆ cycloaliphatic residue and the 3 to 6            membered heterocycloaliphatic residue may in each case may            be unsubstituted or mono- or polysubstituted with at least            one substituent selected from the group consisting of F, Cl,            Br, I, OH, ═O, an O—C₁₋₄ aliphatic residue, OCF₃, CF₃ a            C₁₋₄-aliphatic residue and C(═O)—OH.            In a further preferred embodiment of the compound according            to general formula (I), the residue-   R¹ represents the partial structure (T1),    -   wherein    -   m is 0, 1 or 2 and    -   R^(8a) and R^(8b) each independently of one another represent H,        F, a O—C₁₋₄ aliphatic residue or a C₁₋₄ aliphatic residue;        preferably H, F, CH₃ or OCH₃;    -   R^(8c) denotes a C₁₋₄ aliphatic residue, unsubstituted or mono-        or polysubstituted with at least one substituent selected from        the group consisting of F, Cl, Br, I, an unsubstituted O—C₁₋₄        aliphatic residue, CF₃, and an unsubstituted C₁₋₄-aliphatic        residue,        -   or denotes a C₃₋₁₀-cycloaliphatic residue or a 3 to 10            membered heterocycloaliphatic residue, in each case            unsubstituted or mono- or polysubstituted with at least one            substituent selected from the group consisting of F, Cl, Br,            I, an unsubstituted O—C₁₋₄ aliphatic residue, CF₃, and an            unsubstituted C₁₋₄-aliphatic residue,    -   or    -   wherein    -   m is 0,    -   R^(8a) and R^(8b) each independently of one another represent H,        F, a O—C₁₋₄ aliphatic residue or a C₁₋₄ aliphatic residue;        preferably H, F, CH₃ or OCH₃; and    -   R^(8c) denotes an aryl or heteroaryl, in each case unsubstituted        or mono- or polysubstituted with at least one substituent        selected from the group consisting of F, Cl, Br, I, OH, an        O—C₁₋₄ aliphatic residue, OCF₃, CF₃, CN, a C₁₋₄-aliphatic        residue, C(═O)—CH₃, C(═O)—C₂H₅, C(═O)—O—CH₃, C(═O)—O—C₂H₅ and        phenyl,        -   wherein phenyl may be unsubstituted or mono- or            polysubstituted, preferably unsubstituted or mono- or            disubstituted with at least one substituent selected from            the group consisting of F, Cl, Br, I, OH, an O—C₁₋₄            aliphatic residue, OCF₃, CF₃, CN, a C₁₋₄-aliphatic residue,            O(═O)—CH₃, C(═O)—C₂H₅, C(═O)—O—CH₃ and C(═O)—O—C₂H₅,            preferably with at least one substituent selected from the            group consisting of F, Cl, CH₃, O—CH₃, CF₃ and OCF₃.            Particularly preferred is a compound according to general            formula (I) which has the following general formula (Ie):

In a preferred embodiment of the compound according to general formula(I), the residue

-   R² represents H; F; Cl; Br; I; CN; CF₃; NO₂; OCF₃; SCF₃; a    C₁₋₄-aliphatic residue, a S—C₁₋₄-aliphatic residue, a    O—C₁₋₄-aliphatic residue, wherein the C₁₋₄ aliphatic residue may be    in each case be unsubstituted or mono- or polysubstituted; a    C₃₋₆-cycloaliphatic residue or a 3 to 6 membered    heterocycloaliphatic residue, in each case unsubstituted or mono- or    polysubstituted and in each case optionally bridged via a C₁₋₄    aliphatic group, which in turn may be unsubstituted or mono- or    polysubstituted.

Preferably,

-   R² represents H; F; Cl; Br; I; CN; CF₃; NO₂; OCF₃; SCF₃; a    C₁₋₄-aliphatic residue, a S—C₁₋₄-aliphatic residue, a    O—C₁₋₄-aliphatic residue,    -   wherein the C₁₋₄-aliphatic residue in each case may be        unsubstituted or mono- or polysubstituted with at least one        substituent selected from the group consisting of F, Cl, Br, I,        ═O, OH, and an unsubstituted O—C₁₋₄-aliphatic residue,    -   a C₃₋₆-cycloaliphatic residue or a 3 to 6 membered        heterocycloaliphatic residue, in each case unsubstituted or        mono- or polysubstituted with at least one substituent selected        from the group consisting of F, Cl, Br, I, ═O, OH, a        C₁₋₄-aliphatic residue and a O—C₁₋₄-aliphatic residue,        -   wherein the C₁₋₄-aliphatic residue in each case may be            unsubstituted or mono- or polysubstituted with at least one            substituent selected from the group consisting of F, Cl, Br,            I, ═O, OH, and an unsubstituted O—C₁₋₄-aliphatic residue,    -   and wherein the C₃₋₆-cycloaliphatic residue or the 3 to 6        membered heterocycloaliphatic residue may in each case be        optionally bridged via a C₁₋₄ aliphatic group, which in turn may        be unsubstituted or mono- or polysubstituted with at least one        substituent selected from the group consisting of F, Cl, Br, I,        ═O, OH, an unsubstituted C₁₋₄-aliphatic residue and an        unsubstituted O—C₁₋₄-aliphatic residue.        More preferably,-   R² represents H; F; Cl; Br; I; CN; CF₃; NO₂; OCF₃; SCF₃; a    C₁₋₄-aliphatic residue, a S—C₁₋₄-aliphatic residue, a    O—C₁₋₄-aliphatic residue,    -   wherein the C₁₋₄-aliphatic residue in each case may be        unsubstituted or mono- or polysubstituted with at least one        substituent selected from the group consisting of F, Cl, Br, I,        ═O, OH, and an unsubstituted O—C₁₋₄-aliphatic residue,    -   cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, pyrrolidinyl,        piperazinyl, 4-methylpiperazinyl, morpholinyl, or piperidinyl,        preferably cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl,        in each case unsubstituted or mono- or polysubstituted with at        least one substituent selected from the group consisting of F,        Cl, Br, I, ═O, OH, an unsubstituted C₁₋₄-aliphatic residue and        an unsubstituted O—C₁₋₄-aliphatic residue,    -   and wherein cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,        pyrrolidinyl, piperazinyl, 4-methylpiperazinyl, morpholinyl or        piperidinyl may in each case be optionally bridged via an C₁₋₄        aliphatic group, which in turn may be unsubstituted or mono- or        polysubstituted with at least one substituent selected from the        group consisting of F, Cl, OH, an unsubstituted C₁₋₄-aliphatic        residue and an unsubstituted O—C₁₋₄-aliphatic residue.        Even more preferably,-   R² represents H; F; Cl; Br; I; CN; CF₃; NO₂; OCF₃; SCF₃; methyl;    ethyl; n-propyl; iso-propyl; n-butyl; sec.-butyl; tert.-butyl;    O-methyl; O-ethyl; O—(CH₂)₂—O—CH₃; O—(CH₂)₂—OH; S-Methyl; S-Ethyl;    cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.    Still more preferably,-   R² is selected from the group consisting of H; F; Cl; CF₃; CN; SCF₃;    OCF₃; CH₃; C₂H₅; n-propyl; iso-propyl; t-butyl; cyclopropyl; O—CH₃    and O—C₂H₅;    In particular,-   R² is selected from the group consisting of H; F; Cl; CF₃; CH₃;    C₂H₅, iso-propyl; cyclopropyl; and O—CH₃;    In a particular preferred embodiment of the compound according to    general formula (I), the residue-   R² is ≠H.    In a preferred embodiment of the compound according to general    formula (I), the residues-   R³, R⁴, R⁵ and R⁶ each independently of one another represent H; F;    Cl; Br; I; CN; CF₃; OCF₃; SCF₃; C(═O)H; C(═O)—OH; C(═O)—NH₂;    S(═O)₂—OH; NO₂; a C₁₋₄-aliphatic residue, a C(═O)—C₁₋₄ aliphatic    residue, a C(═O)—O—C₁₋₄ aliphatic residue, a C(═O)—NH—C₁₋₄ aliphatic    residue, a C(═O)—N(C₁₋₄ aliphatic residue)₂, a O—C₁₋₄-aliphatic    residue, a O—C(═O)—C₁₋₄-aliphatic residue, a S—C₁₋₄-aliphatic    residue, a S(═O)₂—C₁₋₄-aliphatic residue, a NH(C₁₋₄ aliphatic    residue), a N(C₁₋₄ aliphatic residue)₂, a NH—C(═O)—C₁₋₄ aliphatic    residue, and a NH—S(═O)₂—C₁₋₄-aliphatic residue, wherein the    C₁₋₄-aliphatic residue in each case may be unsubstituted or mono- or    polysubstituted with at least one substituent selected from the    group consisting of F, Cl, Br, I, ═O, OH, and a O—C₁₋₄-aliphatic    residue; a C₃₋₆-cycloaliphatic residue or a 3 to 6 membered    heterocycloaliphatic residue, in each case unsubstituted or mono- or    polysubstituted with at least one substituent selected from the    group consisting of F, Cl, Br, I, ═O, OH, a C₁₋₄-aliphatic residue    and a O—C₁₋₄-aliphatic residue, and in each case optionally bridged    via an unsubstituted C₁₋₄ aliphatic group,    preferably on the condition that at least one of R³, R⁴, R⁵ and R⁶    is ≠H.

Preferably,

-   R³, R⁴, R⁵ and R⁶ each independently of one another represent H; F;    Cl; Br; I; CN; CF₃; OCF₃; SCF₃; C(═O)H; C(═O)—OH; C(═O)—NH₂;    S(═O)₂—OH; NO₂; a C₁₋₄-aliphatic residue, a C(═O)—C₁₋₄ aliphatic    residue, a C(═O)—O—C₁₋₄ aliphatic residue, a O—C₁₋₄-aliphatic    residue, a O—C(═O)—C₁₋₄-aliphatic residue, a S—C₁₋₄-aliphatic    residue, a S(═O)₂—C₁₋₄-aliphatic residue, wherein the C₁₋₄-aliphatic    residue in each case may be unsubstituted or mono- or    polysubstituted with at least one substituent selected from the    group consisting of F, Cl, Br, I, ═O, OH, and a O—C₁₋₄-aliphatic    residue; a C₃₋₆-cycloaliphatic residue or a 3 to 6 membered    heterocycloaliphatic residue, in each case unsubstituted or mono- or    polysubstituted with at least one substituent selected from the    group consisting of F, Cl, Br, I, ═O, OH, a C₁₋₄-aliphatic residue    and a O—C₁₋₄-aliphatic residue, and in each case optionally bridged    via an unsubstituted C₁₋₄ aliphatic group,    preferably on the condition that at least one of R³, R⁴, R⁵ and R⁶    is ≠H.    More preferably,-   R³, R⁴, R⁵ and R⁶ each independently of one another represent H; F;    Cl; Br; I; CN; CF₃; OCF₃; SCF₃; C(═O)H; NO₂; a C₁₋₄-aliphatic    residue, a C(═O)—C₁₋₄ aliphatic residue, a C(═O)—O—C₁₋₄ aliphatic    residue, a O—C₁₋₄-aliphatic residue, a S—C₁₋₄-aliphatic residue,    wherein the C₁₋₄-aliphatic residue in each case may be unsubstituted    or mono- or polysubstituted with at least one substituent selected    from the group consisting of F, Cl, Br, I, ═O, OH, and a    O—C₁₋₄-aliphatic residue; a C₃₋₆-cycloaliphatic residue,    unsubstituted or mono- or polysubstituted with at least one    substituent selected from the group consisting of F, Cl, Br, I, ═O,    OH, a C₁₋₄-aliphatic residue and a O—C₁₋₄-aliphatic residue, and in    each case optionally bridged via an unsubstituted C₁₋₄ aliphatic    group,    preferably on the condition that at least one of R³, R⁴, R⁵ and R⁶    is ≠H.

In a further preferred embodiment of the present invention

-   R³, R⁴, R⁵ and R⁶ each independently of one another are selected    from the group consisting of H; F; Cl; Br; I; NO₂; CF₃; CN; OCF₃;    SCF₃; a (C═O)—C₁₋₄ aliphatic residue, a C₁₋₄ aliphatic residue,    O—C₁₋₄ aliphatic residue, a S—C₁₋₄ aliphatic residue, wherein the    C₁₋₄-aliphatic residue in each case may be unsubstituted or mono- or    polysubstituted with at least one substituent selected from the    group consisting of F, Cl, and O—CH₃;    preferably on the condition that at least one of R³, R⁴, R⁵ and R⁶    is ≠H.

Preferably,

-   R³, R⁴, R⁵ and R⁶ each independently of one another are selected    from the group consisting of H; F; Cl; Br; I; NO₂; CF₃; CN; OCF₃;    SCF₃; methyl; ethyl; n-propyl; iso-propyl; n-butyl; sec.-butyl;    tert.-butyl; cyclopropyl; C(═O)-methyl; C(═O)-ethyl;    (C═O)-isopropyl; (C═O)-t-butyl; O-methyl; O-ethyl; O-isopropyl;    O-t-butyl; O—(CH₂)₂—O—CH₃; S-Methyl; S-Ethyl;    preferably on the condition that at least one of R³, R⁴, R⁵ and R⁶    is ≠H.    In particular,-   R³, R⁴, R⁵ and R⁶ are each independently of one another are selected    from the group consisting of H; F; Cl; Br; I; NO₂; CF₃; CN;    (C═O)-methyl; (C═O)-ethyl; (C═O)-isopropyl; (C═O)-t-butyl; methyl;    ethyl; isopropyl; t-butyl; O-methyl; O-Ethyl; O-isopropyl;    O-t-butyl; OCF₃; S-methyl; S-ethyl; and SCF₃;    preferably on the condition that at least one of R³, R⁴, R⁵ and R⁶    is ≠H.    More particularly,-   R³, R⁴, R⁵ and R⁶ are each independently of one another selected    from the group consisting of H; F; Cl; Br; CF₃; CN; OCF₃ and NO₂;    preferably on the condition that at least one of R³, R⁴, R⁵ and R⁶    is ≠H.    Most preferred,-   R³, R⁴ and R⁶ each independently of one another are selected from    the group consisting of H and F; and-   R⁵ denotes F; Br; CF₃; OCF₃; CN; or NO₂;

In a particular preferred embodiment of the compound according togeneral formula (I)

at least one of the residues R³, R⁴, R⁵ and R⁶ is ≠H.

In a preferred embodiment of the compound according to general formula(I), the residue

-   R⁷ denotes a C₁₋₁₀-aliphatic residue, preferably a C₁₋₈-aliphatic    residue, unsubstituted or mono- or polysubstituted with at least one    substituent selected from the group consisting of F, Cl, Br, I, NO₂,    NH₂, an NH(C₁₋₄ aliphatic residue), an N(C₁₋₄ aliphatic residue)₂,    OH, ═O, an O—C₁₋₄-aliphatic residue, OCF₃, SH, SCF₃, a    S—C₁₋₄-aliphatic residue, CF₃, CN, a C₁₋₄-aliphatic residue, a    C(═O)—O—C₁₋₄-aliphatic residue, and C(═O)—OH,    -   wherein the C₁₋₄-aliphatic residue in each case may be        unsubstituted or mono- or polysubstituted with at least one        substituent selected from the group consisting of F, Cl, Br, I,        OH, OCF₃, CF₃ and an unsubstituted O—C₁₋₄-aliphatic residue,    -   or denotes a C₃₋₄₀-cycloaliphatic residue or a 3 to 10 membered        heterocycloaliphatic residue, in each case unsubstituted or        mono- or polysubstituted with at least one substituent selected        from the group consisting of F, Cl, Br, I, NO₂, NH₂, an NH(C₁₋₄        aliphatic residue), an N(C₁₋₄ aliphatic residue)₂, OH, ═O, an        O—C₁₋₄ aliphatic residue, OCF₃, SH, SCF₃, a S—C₁₋₄ aliphatic        residue, CF₃, CN, a C₁₋₄-aliphatic residue, C(═O)—OH, a        C(═O)—O—C₁₋₄-aliphatic residue a C₃₋₆ cycloaliphatic residue,        and a 3 to 6 membered heterocycloaliphatic residue,        -   wherein the C₁₋₄-aliphatic residue in each case may be            unsubstituted or mono- or polysubstituted with at least one            substituent selected from the group consisting of F, Cl, Br,            I, OH, OCF₃, CF₃ and an unsubstituted O—C₁₋₄-aliphatic            residue, and        -   wherein the C₃₋₆ cycloaliphatic residue and the 3 to 6            membered heterocycloaliphatic residue may in each case may            be unsubstituted or mono- or polysubstituted with at least            one substituent selected from the group consisting of F, Cl,            Br, I, NO₂, NH₂, an NH(C₁₋₄ aliphatic residue), an N(C₁₋₄            aliphatic residue)₂, OH, ═O, an O—C₁₋₄ aliphatic residue,            OCF₃, SH, SCF₃, a S—C₁₋₄ aliphatic residue, CF₃, CN, a            C₁₋₄-aliphatic residue and C(═O)—OH,    -   and wherein the C₃₋₁₀-cycloaliphatic residue or the 3 to 10        membered heterocycloaliphatic residue may in each case        optionally bridged via a C₁₋₈ aliphatic group, preferably a C₁₋₄        aliphatic group, which in turn may be unsubstituted or mono- or        polysubstituted with at least one substituent selected from the        group consisting of F, Cl, Br, I, NO₂, NH₂, an NH(C₁₋₄ aliphatic        residue), an N(C₁₋₄ aliphatic residue)₂, OH, ═O, an O—C₁₋₄        aliphatic residue, a C(═O)—O—C₁₋₄-aliphatic residue, OCF₃, SH,        SCF₃, a S—C₁₋₄ aliphatic residue, CF₃, CN, a C₁₋₄-aliphatic        residue and C(═O)—OH,    -   on the condition that if R⁷ denotes a 3 to 10 membered        heterocycloaliphatic residue, the 3 to 10 membered        heterocycloaliphatic residue is linked via a carbon atom.        In a further preferred embodiment of the compound according to        general formula (I), the residue-   R⁷ denotes a C₁₋₁₀-aliphatic residue, preferably a C₁₋₈-aliphatic    residue, unsubstituted or mono- or polysubstituted with at least one    substituent selected from the group consisting of F, Cl, Br, I, NO₂,    OH, ═O, an O—C₁₋₄-aliphatic residue, OCF₃, SH, SCF₃, a    S—C₁₋₄-aliphatic residue, a C(═O)—O—C₁₋₄-aliphatic residue, CF₃, CN,    and a C₁₋₄-aliphatic residue    -   wherein the C₁₋₄-aliphatic residue in each case may be        unsubstituted or mono- or polysubstituted with at least one        substituent selected from the group consisting of F, Cl, Br, I,        OH, OCF₃, CF₃ and an unsubstituted O—C₁₋₄-aliphatic residue,    -   or denotes a C₃₋₁₀-cycloaliphatic residue or a 3 to 10 membered        heterocycloaliphatic residue, in each case unsubstituted or        mono- or polysubstituted with at least one substituent selected        from the group consisting of F, Cl, Br, I, NO₂, OH, ═O, an        O—C₁₋₄ aliphatic residue, OCF₃, SH, SCF₃, a S—C₁₋₄ aliphatic        residue, a C(═O)—O—C₁₋₄-aliphatic residue, CF₃, CN, a        C₁₋₄-aliphatic residue, a C₃₋₆ cycloaliphatic residue, and a 3        to 6 membered heterocycloaliphatic residue,        -   wherein the C₁₋₄-aliphatic residue in each case may be            unsubstituted or mono- or polysubstituted with at least one            substituent selected from the group consisting of F, Cl, Br,            I, OH, OCF₃, CF₃ and an unsubstituted O—C₁₋₄-aliphatic            residue, and        -   wherein the C₃₋₆ cycloaliphatic residue and the 3 to 6            membered heterocycloaliphatic residue may in each case may            be unsubstituted or mono- or polysubstituted with at least            one substituent selected from the group consisting of F, Cl,            Br, I, NO₂, OH, ═O, an O—C₁₋₄ aliphatic residue, OCF₃, SH,            SCF₃, a S—C₁₋₄ aliphatic residue, CF₃, CN, and a            C₁₋₄-aliphatic residue,    -   and wherein the C₃₋₁₀-cycloaliphatic residue or the 3 to 10        membered heterocycloaliphatic residue may in each case        optionally bridged via a C₁₋₈ aliphatic group, preferably a C₁₋₄        aliphatic group, which in turn may be unsubstituted or mono- or        polysubstituted with at least one substituent selected from the        group consisting of F, Cl, Br, I, NO₂, OH, ═O, an O—C₁₋₄        aliphatic residue, a C(═O)—O—C₁₋₄-aliphatic residue, OCF₃, SH,        SCF₃, a S—C₁₋₄ aliphatic residue, CF₃, CN, and a C₁₋₄-aliphatic        residue.    -   on the condition that if R⁷ denotes a 3 to 10 membered        heterocycloaliphatic residue, the 3 to 10 membered        heterocycloaliphatic residue is linked via a carbon atom.

Preferably,

-   R⁷ denotes a C₁₋₈-aliphatic residue, unsubstituted or mono- or    polysubstituted with at least one substituent selected from the    group consisting of F, Cl, Br, I, OH, ═O, an O—C₁₋₄-aliphatic    residue, OCF₃, SH, SCF₃, a S—C₁₋₄-aliphatic residue, a    C(═O)—O—C₁₋₄-aliphatic residue, CF₃, and a C₁₋₄-aliphatic residue    -   wherein the C₁₋₄-aliphatic residue in each case may be        unsubstituted or mono- or polysubstituted with at least one        substituent selected from the group consisting of F, Cl, Br, I,        OH, CF₃ and an unsubstituted O—C₁₋₄-aliphatic residue,    -   or denotes a C₃₋₁₀-cycloaliphatic residue or a 3 to 10 membered        heterocycloaliphatic residue, in each case unsubstituted or        mono- or polysubstituted with at least one substituent selected        from the group consisting of F, Cl, Br, I, OH, ═O, an O—C₁₋₄        aliphatic residue, OCF₃, SCF₃, a C(═O)—O—C₁₋₄-aliphatic residue,        a S—C₁₋₄ aliphatic residue, CF₃, and a C₁₋₄-aliphatic residue,        -   wherein the C₁₋₄-aliphatic residue in each case may be            unsubstituted or mono- or polysubstituted with at least one            substituent selected from the group consisting of F, Cl, Br,            I, OH, OCF₃, CF₃ and an unsubstituted O—C₁₋₄-aliphatic            residue, and    -   and wherein the C₃₋₁₀-cycloaliphatic residue or the 3 to 10        membered heterocycloaliphatic residue may in each case        optionally bridged via a C₁₋₈ aliphatic group, preferably a C₁₋₄        aliphatic group, which in turn may be unsubstituted or mono- or        polysubstituted with at least one substituent selected from the        group consisting of F, Cl, Br, I, OH, ═O, an O—C₁₋₄ aliphatic        residue, OCF₃, SH, SCF₃, a S—C₁₋₄ aliphatic residue, a        C(═O)—O—C₁₋₄-aliphatic residue, CF₃, CN, and a C₁₋₄-aliphatic        residue.

on the condition that if R⁷ denotes a 3 to 10 memberedheterocycloaliphatic residue, the 3 to 10 membered heterocycloaliphaticresidue is linked via a carbon atom.

More preferably,

-   R⁷ denotes a C₁₋₈-aliphatic residue, preferably a C₁₋₈-aliphatic    residue, unsubstituted or mono- or polysubstituted with at least one    substituent selected from the group consisting of F, Cl, Br, I, OH,    ═O, an O—C₁₋₄-aliphatic residue, OCF₃, SH, SCF₃, a S—C₁₋₄-aliphatic    residue, CF₃, a C(═O)—O—C₁₋₄-aliphatic residue, and a C₁₋₄-aliphatic    residue    -   wherein the C₁₋₄-aliphatic residue in each case may be        unsubstituted or mono- or polysubstituted with at least one        substituent selected from the group consisting of F, Cl, Br, I,        OH, CF₃ and an unsubstituted O—C₁₋₄-aliphatic residue,    -   or denotes a C₃₋₁₀-cycloaliphatic residue or a 3 to 10 membered        heterocycloaliphatic residue, in each case unsubstituted or        mono- or polysubstituted with at least one substituent selected        from the group consisting of F, Cl, Br, I, OH, ═O, an O—C₁₋₄        aliphatic residue, OCF₃, SCF₃, a S—C₁₋₄ aliphatic residue, a        C(═O)—O—C₁₋₄-aliphatic residue, CF₃, and a C₁₋₄-aliphatic        residue,        -   wherein the C₁₋₄-aliphatic residue in each case may be            unsubstituted or mono- or polysubstituted with at least one            substituent selected from the group consisting of F, Cl, Br,            I, OH, OCF₃, CF₃ and an unsubstituted O—C₁₋₄-aliphatic            residue, and    -   wherein the C₃₋₁₀-cycloaliphatic residue or the 3 to 10 membered        heterocycloaliphatic residue is bridged via a C₁₋₈ aliphatic        group, preferably a C₁₋₄ aliphatic group, which in turn may be        unsubstituted or mono- or polysubstituted with at least one        substituent selected from the group consisting of F, Cl, Br, I,        OH, ═O, an O—C₁₋₄ aliphatic residue, OCF₃, SH, SCF₃, a S—C₁₋₄        aliphatic residue, a C(═O)—O—C₁₋₄-aliphatic residue, CF₃, CN,        and a C₁₋₄-aliphatic residue.        Even more preferably,-   R⁷ denotes a C₁₋₈-aliphatic residue, preferably a C₁₋₈-aliphatic    residue, unsubstituted or mono- or polysubstituted with at least one    substituent selected from the group consisting of F, Cl, Br, I, OH,    ═O, an O—C₁₋₄-aliphatic residue, OCF₃, SH, SCF₃, a S—C₁₋₄-aliphatic    residue, a C(═O)—O—C₁₋₄-aliphatic residue, CF₃, and a C₁₋₄-aliphatic    residue    -   wherein the C₁₋₄-aliphatic residue in each case may be        unsubstituted or mono- or polysubstituted with at least one        substituent selected from the group consisting of F, Cl, Br, I,        OH, CF₃ and an unsubstituted O—C₁₋₄-aliphatic residue,    -   or denotes a C₃₋₁₀-cycloaliphatic residue or a 3 to 10 membered        heterocycloaliphatic residue, in each case unsubstituted or        mono- or polysubstituted with at least one substituent selected        from the group consisting of F, Cl, Br, I, OH, ═O, an O—C₁₋₄        aliphatic residue, OCF₃, SCF₃, a S—C₁₋₄ aliphatic residue, a        C(═O)—O—C₁₋₄-aliphatic residue, CF₃, and a C₁₋₄-aliphatic        residue,        -   wherein the C₁₋₄-aliphatic residue in each case may be            unsubstituted or mono- or polysubstituted with at least one            substituent selected from the group consisting of F, Cl, Br,            I, OH, OCF₃, CF₃ and an unsubstituted O—C₁₋₄-aliphatic            residue, and    -   wherein the C₃₋₁₀-cycloaliphatic residue or the 3 to 10 membered        heterocycloaliphatic residue is in each case bridged via a        unsubstituted C₁₋₈ aliphatic group, preferably an unsubstituted        C₁₋₄ aliphatic group.        Still more preferably,-   R⁷ denotes a C₁₋₆-aliphatic residue, unsubstituted or mono- or    polysubstituted with at least one substituent selected from the    group consisting of F, Cl, Br, I, OH, ═O, an O—C₁₋₄-aliphatic    residue, a C(═O)—O—C₁₋₄-aliphatic residue, OCF₃, SH, SCF₃, a    S—C₁₋₄-aliphatic residue, CF₃, and a C₁₋₄-aliphatic residue    -   wherein the C₁₋₄-aliphatic residue in each case is        unsubstituted,    -   or denotes a C₃₋₁₀-cycloaliphatic residue or a 3 to 10 membered        heterocycloaliphatic residue, in each case unsubstituted or        mono- or polysubstituted with at least one substituent selected        from the group consisting of F, Cl, Br, I, OH, ═O, an O—C₁₋₄        aliphatic residue, OCF₃, SCF₃, a S—C₁₋₄ aliphatic residue, a        C(═O)—O—C₁₋₄-aliphatic residue, CF₃, and a C₁₋₄-aliphatic        residue,        -   wherein the C₁₋₄-aliphatic residue in each case may be            unsubstituted or mono- or polysubstituted with OH or an            unsubstituted O—C₁₋₄-aliphatic residue.    -   and wherein the C₃₋₁₀-cycloaliphatic residue or the 3 to 10        membered heterocycloaliphatic residue is in each case bridged        via a unsubstituted C₁₋₄ aliphatic group        In particular,-   R⁷ denotes a C₁₋₆-aliphatic residue, unsubstituted or mono- or    polysubstituted with at least one substituent selected from the    group consisting of F, Cl, Br, I, OH, ═O, an O—C₁₋₄-aliphatic    residue, a C(═O)—O—C₁₋₄-aliphatic residue, OCF₃, SH, SCF₃, a    S—C₁₋₄-aliphatic residue, CF₃, and a C₁₋₄-aliphatic residue    -   wherein the C₁₋₄-aliphatic residue in each case is        unsubstituted.        Most preferred,-   R⁷ denotes a C₁₋₆-aliphatic residue, unsubstituted or mono- or    polysubstituted with at least one substituent selected from the    group consisting of F, CF₃, Cl, OH, and O-methyl.    Preferred is also a compound according to general formula (I),    wherein-   R¹ represents the partial structure (T1),

-   -   wherein    -   m is 0, 1 or 2 and    -   R^(8a) and R^(8b) each independently of one another represent H,        F, a O—C₁₋₄ aliphatic residue or a C₁₋₄ aliphatic residue;        preferably H, F, CH₃ or OCH₃;    -   R^(8c) denotes a C₁₋₄ aliphatic residue, unsubstituted or mono-        or polysubstituted with at least one substituent selected from        the group consisting of F, Cl, Br, I, an unsubstituted O—C₁₋₄        aliphatic residue, CF₃, and an unsubstituted C₁₋₄-aliphatic        residue,        -   or denotes a C₃₋₁₀-cycloaliphatic residue or a 3 to 10            membered heterocycloaliphatic residue, in each case            unsubstituted or mono- or polysubstituted with at least one            substituent selected from the group consisting of F, Cl, Br,            I, an unsubstituted O—C₁₋₄ aliphatic residue, CF₃, and an            unsubstituted C₁₋₄-aliphatic residue,    -   or    -   wherein    -   m is 0,    -   R^(8a) and R^(8b) each independently of one another represent H,        F, a O—C₁₋₄ aliphatic residue or a C₁₋₄ aliphatic residue;        preferably H, F, CH₃ or OCH₃; and    -   R^(8c) denotes an aryl or heteroaryl, in each case unsubstituted        or mono- or polysubstituted with at least one substituent        selected from the group consisting of F, Cl, Br, I, OH, an        O—C₁₋₄ aliphatic residue, OCF₃, CF₃, CN, a C₁₋₄-aliphatic        residue, C(═O)—CH₃, C(═O)—C₂H₅, C(═O)—O—CH₃, C(═O)—O—C₂H₅ and        phenyl,        -   wherein phenyl may be unsubstituted or mono- or            polysubstituted, preferably unsubstituted or mono- or            disubstituted with at least one substituent selected from            the group consisting of F, Cl, Br, I, OH, an O—C₁₋₄            aliphatic residue, OCF₃, CF₃, CN, a C₁₋₄-aliphatic residue,            C(═O)—CH₃, C(═O)—C₂H₅, C(═O)—O—CH₃ and C(═O)—O—C₂H₅,            preferably with at least one substituent selected from the            group consisting of F, Cl, CH₃, O—CH₃, CF₃ and OCF₃,

-   R² is selected from the group consisting of H; F; Cl; CF₃; CH₃;    C₂H₅, iso-propyl; cyclopropyl; and O—CH₃;

-   R³, R⁴, R⁵ and R⁶ are each independently of one another selected    from the group consisting of H; F; Cl; Br; CF₃; CN; OCF₃ and NO₂;    preferably on the condition that at least one of R³, R⁴, R⁵ and R⁶    is ≠H,

-   R⁷ denotes a C₁₋₆-aliphatic residue, unsubstituted or mono- or    polysubstituted with at least one substituent selected from the    group consisting of F, Cl, Br, I, OH, ═O, an O—C₁₋₄-aliphatic    residue, a C(═O)—O—C₁₋₄-aliphatic residue, OCF₃, SH, SCF₃, a    S—C₁₋₄-aliphatic residue, CF₃, and a C₁₋₄-aliphatic residue    -   wherein the C₁₋₄-aliphatic residue in each case is        unsubstituted.        Particularly preferred is also a compound according to general        formula (I), wherein

-   R¹ represents aryl, preferably phenyl, or heteroaryl, preferably    pyridyl or thienyl, in each case unsubstituted or mono- or    disubstituted with at least one substituent selected from the group    consisting of F, Cl, Br, I, OH, OCH₃, OCF₃, CF₃, CN, and CH₃,    -   preferably represents phenyl, unsubstituted or mono- or        disubstituted with at least one substituent selected from the        group consisting of F, Cl, Br, I, OH, OCH₃, OCF₃, CF₃, CN, and        CH₃;

-   R² is selected from the group consisting of H, F, Cl, CF₃, CH₃,    C₂H₅, iso-propyl, cyclopropyl, and O—CH₃; preferably is selected    from the group consisting of CH₃, C₂H₅, OCH₃ and CF₃;

-   R³, R⁴, R⁵ and R⁶ are each independently of one another selected    from the group consisting of H, F, Cl, Br, CF₃, CN, OCF₃ and NO₂;    preferably on the condition that at least one of R³, R⁴, R⁵ and R⁶    is ≠H, more preferably on the condition that R⁵ is ≠H;

-   R⁷ denotes a saturated C₁₋₄-aliphatic residue, unsubstituted or    mono- or disubstituted with at least one substituent selected from    the group consisting of F, Cl, Br, I, OH, O—CH₃, OCF₃, SCF₃, and    CF₃.    Especially particularly preferred are compounds according to general    formula (I) selected from the group comprising:

-   1    N-(3,3-dimethyl-butyl)-2-methoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylic    acid amide;

-   2    2-ethoxy-4-methyl-N-(thiophene-2-yl-methyl)-7-(trifluoromethyl)-quinoline-3-carboxylic    acid amide;

-   3    2-ethoxy-N-[(4-fluorophenyl)-methyl]-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylic    acid amide;

-   4    N-[(3-fluorophenyl)-methyl]-2-methoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylic    acid amide;

-   5    N-[(4-fluorophenyl)-methyl]-2-methoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylic    acid amide;

-   6    2-ethoxy-N-[(3-fluorophenyl)-methyl]-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylic    acid amide;

-   7    N-[(3-fluorophenyl)-methyl]-2-(2-methoxy-ethoxy)-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylic    acid amide;

-   8    N-[(4-fluorophenyl)-methyl]-2-(2-methoxy-ethoxy)-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylic    acid amide;

-   9    N-[(3-fluorophenyl)-methyl]-2-(2-hydroxy-ethoxy)-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylic    acid amide;

-   10    N-[(3-fluorophenyl)-methyl]-2-isopropoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylic    acid amide;

-   11    N-[(4-fluorophenyl)-methyl]-2-isopropoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylic    acid amide;

-   12    2-ethoxy-N-[(3-fluorophenyl)-methyl]-4-methoxy-7-(trifluoremethyl)-quinoline-3-carboxylic    acid amide;

-   13    N-[(3-fluorophenyl)-methyl]-2,4-dimethoxy-7-(trifluoromethyl)-quinoline-3-carboxylic    acid amide;

-   14    2-ethoxy-N-[(4-fluorophenyl)-methyl]-4-methoxy-7-(trifluoromethyl)-quinoline-3-carboxylic    acid amide;

-   15    2-ethoxy-6,7-difluoro-N-[(3-fluorophenyl)-methyl]-4-methoxy-quinoline-3-carboxylic    acid amide;

-   16    N-[(4-fluorophenyl)-methyl]-2,4-dimethoxy-7-(trifluoromethyl)-quinoline-3-carboxylic    acid amide;

-   17    6,7-difluoro-N-[(3-fluorophenyl)-methyl]-2,4-dimethoxy-quinoline-3-carboxylic    acid amide;

-   18    7-fluoro-N-[(3-fluorophenyl)-methyl]-2-methoxy-4-methyl-quinoline-3-carboxylic    acid amide;

-   19    N-[(3-fluoro-4-methyl-phenyl)-methyl]-2-methoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylic    acid amide;

-   20    2-ethoxy-N-[(3-fluoro-4-methyl-phenyl)-methyl]-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylic    acid amide;

-   21    2-methoxy-4-methyl-N-(m-tolyl-methyl)-7-(trifluoromethyl)-quinoline-3-carboxylic    acid amide;

-   22    2-ethoxy-4-methyl-N-(m-tolyl-methyl)-7-(trifluoromethyl)-quinoline-3-carboxylic    acid amide;

-   23    N-[(4-fluoro-3-methyl-phenyl)-methyl]-2-methoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylic    acid amide;

-   24    2-ethoxy-N-[(4-fluoro-3-methyl-phenyl)-methyl]-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylic    acid amide;

-   25    2-methoxy-4-methyl-N-(p-tolyl-methyl)-7-(trifluoromethyl)-quinoline-3-carboxylic    acid amide;

-   26    2-ethoxy-4-methyl-N-(p-tolyl-methyl)-7-(trifluoromethyl)-quinoline-3-carboxylic    acid amide;

-   27    2-ethoxy-4-methyl-N-(4-methyl-pentyl)-7-(trifluoromethyl)-quinoline-3-carboxylic    acid amide;

-   28    2-methoxy-4-methyl-N-(4-methyl-pentyl)-7-(trifluoromethyl)-quinoline-3-carboxylic    acid amide;

-   29    N-(4,4-dimethyl-pentyl)-2-methoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylic    acid amide;

-   30    N-(4,4-dimethyl-pentyl)-2-ethoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylic    acid amide;

-   31    7-bromo-2-ethoxy-N-[(4-fluorophenyl)-methyl]-4-methyl-quinoline-3-carboxylic    acid amide;

-   32    7-bromo-2-ethoxy-N-[(3-fluorophenyl)-methyl]-4-methyl-quinoline-3-carboxylic    acid amide;

-   33    7-bromo-N-[(3-fluorophenyl)-methyl]-2-methoxy-4-methyl-quinoline-3-carboxylic    acid amide;

-   34    7-bromo-N-[(4-fluorophenyl)-methyl]-2-methoxy-4-methyl-quinoline-3-carboxylic    acid amide;

-   35    7-cyano-2-ethoxy-N-[(4-fluorophenyl)-methyl]-4-methyl-quinoline-3-carboxylic    acid amide;

-   36    7-cyano-2-ethoxy-N-[(3-fluorophenyl)-methyl]-4-methyl-quinoline-3-carboxylic    acid amide;

-   37    7-cyano-N-[(3-fluorophenyl)-methyl]-2-methoxy-4-methyl-quinoline-3-carboxylic    acid amide;

-   38    7-cyano-N-[(4-fluorophenyl)-methyl]-2-methoxy-4-methyl-quinoline-3-carboxylic    acid amide;

-   39    N-[(3-fluoro-2-methoxy-phenyl)-methyl]-2-methoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylic    acid amide;

-   40    N-[(3-fluoro-5-methoxy-phenyl)-methyl]-2-methoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylic    acid amide;

-   41    N-[(5-fluoro-2-methoxy-phenyl)-methyl]-2-methoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylic    acid amide;

-   42    N-[(3-fluoro-2-hydroxy-phenyl)-methyl]-2-methoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylic    acid amide;

-   43    N-[(3-fluoro-5-hydroxy-phenyl)-methyl]-2-methoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylic    acid amide;

-   44    N-[(5-fluoro-2-hydroxy-phenyl)-methyl]-2-methoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylic    acid amide;

-   45    N-[(3-fluoro-4-hydroxy-phenyl)-methyl]-2-methoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylic    acid amide;

-   46    7-fluoro-N-[(4-fluorophenyl)-methyl]-2-methoxy-4-methyl-quinoline-3-carboxylic    acid amide:

-   47    5,7-difluoro-N-[(3-fluorophenyl)-methyl]-2-methoxy-4-methyl-quinoline-3-carboxylic    acid amide;

-   48    6,7-difluoro-N-[(3-fluorophenyl)-methyl]-2-methoxy-4-methyl-quinoline-3-carboxylic    acid amide;

-   49    7,8-difluoro-N-[(3-fluorophenyl)-methyl]-2-methoxy-4-methyl-quinoline-3-carboxylic    acid amide;

-   50    N-[(3-fluorophenyl)-methyl]-4-methyl-2-(2,2,2-trifluoro-ethoxy)-7-(trifluoromethyl)-quinoline-3-carboxylic    acid amide;

-   51    N-[(3-fluorophenyl)-methyl]-2-methoxy-4-(trifluoromethyl)-quinoline-3-carboxylic    acid amide;

-   52    2-ethoxy-N-[(3-fluorophenyl)-methyl]-4-(trifluoromethyl)-quinoline-3-carboxylic    acid amide; and

-   53    N-[(3-fluorophenyl)-methyl]-2-isopropoxy-4-(trifluoromethyl)-quinoline-3-carboxylic    acid amide;    respectively in the form of the free compounds; the racemate; the    enantiomers, diastereomers, mixtures of the enantiomers or    diastereomers in any mixing ratio or of an individual enantiomer or    diastereomer; or in the form of the salts of physiologically    acceptable acids or bases; or in the form of solvates, in particular    hydrates.

The substituted compounds according to the invention of theaforementioned general formula (I) and corresponding stereoisomers andalso the respective corresponding salts and solvates are toxicologicallysafe and are therefore suitable as pharmaceutical active ingredients inpharmaceutical compositions.

The present invention therefore further relates to a pharmaceuticalcomposition containing at least one compound according to generalformula (I), in each case if appropriate optionally in the form of oneof its pure stereoisomers, in particular enantiomers or diastereomers,its racemates or in the form of a mixture of stereoisomers, inparticular the enantiomers and/or diastereomers, in any desired mixingratio, or respectively in the form of a physiologically acceptable salt,or respectively in the form of a corresponding solvate, and also ifappropriate optionally at least one pharmaceutically acceptableauxiliary and/or optionally at least one further active ingredient.

These pharmaceutical compositions according to the invention aresuitable in particular for the modulation of KCNQ2/3 K⁺ channels,preferably for KCNQ2/3 K⁺ channel inhibition and/or KCNQ2/3 K⁺ channelstimulation, i.e. they exert an agonistic or antagonistic effect.

Likewise, the pharmaceutical compositions according to the invention arepreferably suitable for the prophylaxis and/or treatment of disordersand/or diseases which are mediated, at least in part, by KCNQ2/3 K⁺channels.

The pharmaceutical composition according to the invention is suitablefor administration to adults and children, including toddlers andbabies.

The pharmaceutical composition according to the invention may beprepared as a liquid, semisolid or solid pharmaceutical form, forexample in the form of injection solutions, drops, juices, syrups,sprays, suspensions, tablets, patches, capsules, plasters,suppositories, ointments, creams, lotions, gels, emulsions, aerosols orin multiparticulate form, for example in the form of pellets orgranules, if appropriate pressed into tablets, decanted in capsules orsuspended in a liquid, and also be administered as much.

In addition to at least one substituted compound of general formula (I),if appropriate in the form of one of its pure stereoisomers, inparticular enantiomers or diastereomers, its racemate or in the form ofmixtures of the stereoisomers, in particular the enantiomers ordiastereomers, in any desired mixing ratio, or if appropriate in theform of a corresponding salt or respectively in the form of acorresponding solvate, the pharmaceutical composition according to theinvention conventionally may contain further physiologically acceptablepharmaceutical auxiliaries which, for example, can be selected from thegroup consisting of excipients, fillers, solvents, diluents,surface-active substances, dyes, preservatives, blasting agents, slipadditives, lubricants, aromas and binders.

The selection of the physiologically acceptable auxiliaries and also theamounts thereof to be used depend on whether the pharmaceuticalcomposition is to be applied orally, subcutaneously, parenterally,intravenously, intraperitoneally, intradermally, intramuscularly,intranasally, buccally, rectally or locally, for example to infectionsof the skin, the mucous membranes and of the eyes. Preparations in theform of tablets, dragées, capsules, granules, pellets, drops, juices andsyrups are preferably suitable for oral application; solutions,suspensions, easily reconstitutable dry preparations and also sprays arepreferably suitable for parenteral, topical and inhalative application.The substituted compounds according to the invention used in thepharmaceutical composition according to the invention in a repository,in a dissolved form or in a plaster, and further agents promoting skinpenetration being added if appropriate, are suitable percutaneousapplication preparations. Orally or percutaneously applicablepreparation forms can release the respective substituted compoundaccording to the invention also in a delayed manner.

The pharmaceutical compositions according to the invention can beprepared with the aid of conventional means, devices, methods andprocess known in the art, such as are described for example in“Remington's Pharmaceutical Sciences”, A. R. Gennaro (Editor), 17^(th)edition, Mack Publishing Company, Easton, Pa, 1985, in particular inPart 8, Chapters 76 to 93. The corresponding description is introducedherewith by way of reference and forms part of the disclosure. Theamount to be administered to the patient of the respective substitutedcompounds according to the invention of the above-indicated generalformula (I) may vary and is for example dependent on the patient'sweight or age and also on the type of application, the indication andthe severity of the disorder. Conventionally, 0.001 to 100 mg/kg,preferably 0.05 to 75 mg/kg, particularly preferably 0.05 to 50 mg of atleast one compound according to the invention are applied per kg of thepatient's body weight.

The pharmaceutical composition according to the invention is preferablysuitable for the treatment and/or prophylaxis of one or more diseasesand/or disorders selected from the group consisting of pain, inparticular pain selected from the group consisting of acute pain,chronic pain, neuropathic pain, muscular pain, visceral pain andinflammatory pain, epilepsy, urinary incontinence, anxiety, dependency,mania, bipolar disorders, migraine, cognitive diseases anddystonia-associated dyskinesias.

The pharmaceutical composition according to the invention is suitableparticularly preferably for the treatment of pain, more particularlypreferably of acute pain, chronic pain, neuropathic pain, visceral pain,inflammatory pain and muscular pain, and most particularly for thetreatment of neuropathic pain.

The pharmaceutical composition according to the invention is alsopreferably suitable for the treatment and/or prophylaxis of epilepsy.

The present invention therefore further relates to at least one compoundaccording to general formula (I) and also if appropriate of one or morepharmaceutically acceptable auxiliaries for use in the modulation ofKCNQ2/3 K⁺ channels, preferably for use in KCNQ2/3 K⁺ channel inhibitionand/or stimulation.

The present invention therefore further relates to at least one compoundaccording to general formula (I) and also if appropriate of one or morepharmaceutically acceptable auxiliaries for use in the prophylaxisand/or treatment of disorders and/or diseases which are mediated, atleast in part, by KCNQ2/3 K⁺ channels.

Preference is given to at least one compound according to generalformula (I) and optionally one or more pharmaceutically acceptableauxiliaries for use in the prophylaxis and/or treatment of disordersand/or diseases selected from the group consisting of pain, inparticular pain selected from the group consisting of acute pain,chronic pain, neuropathic pain, muscular pain, visceral pain andinflammatory pain, epilepsy, urinary incontinence, anxiety, dependency,mania, bipolar disorders, migraine, cognitive diseases anddystonia-associated dyskinesias.

Particular preference is given to at least one compound according togeneral formula (I) and optionally one or more pharmaceuticallyacceptable auxiliaries for use in the prophylaxis and/or treatment ofdisorders and/or diseases selected from the group consisting of pain, inparticular pain selected from the group consisting of acute pain,chronic pain, neuropathic pain, muscular pain, visceral pain andinflammatory pain, most particularly neuropathic pain.

Particular preference is also given to at least one compound accordingto general formula (I) and optionally one or more pharmaceuticallyacceptable auxiliaries for use in the prophylaxis and/or treatment ofepilepsy.

The present invention therefore further relates to at least one compoundaccording to general formula (I) and also if appropriate of one or morepharmaceutically acceptable auxiliaries for the modulation of KCNQ2/3 K⁺channels, preferably for KCNQ2/3 K⁺ channel inhibition and/orstimulation.

The present invention therefore further relates to at least one compoundaccording to general formula (I) and also if appropriate of one or morepharmaceutically acceptable auxiliaries for the prophylaxis and/ortreatment of disorders and/or diseases which are mediated, at least inpart, by KCNQ2/3 K⁺ channels.

Preference is given to at least one compound according to generalformula (I) and optionally one or more pharmaceutically acceptableauxiliaries for the prophylaxis and/or treatment of disorders and/ordiseases selected from the group consisting of pain, especially painselected from the group consisting of acute pain, chronic pain,neuropathic pain, muscular pain, visceral pain and inflammatory pain,epilepsy, urinary incontinence, anxiety, dependency, mania, bipolardisorders, migraine, cognitive diseases and dystonia-associateddyskinesias.

Particular preference is given to at least one compound according togeneral formula (I) and optionally one or more pharmaceuticallyacceptable auxiliaries for the prophylaxis and/or treatment of disordersand/or diseases selected from the group consisting of pain, inparticular pain selected from the group consisting of acute pain,chronic pain, neuropathic pain, muscular pain, visceral pain andinflammatory pain, most particularly neuropathic pain.

Particular preference is also given to at least one compound accordingto general formula (I) and optionally one or more pharmaceuticallyacceptable auxiliaries for the prophylaxis and/or treatment of epilepsy.

Another aspect of the present invention is a method of treatment and/orprophylaxis of disorders and/or diseases, which are mediated, at leastin part, by KCNQ2/3 K⁺ channels, in a mammal, preferably of disordersand/or diseases selected from the group consisting of pain, preferablypain selected from the group consisting of acute pain, chronic pain,neuropathic pain, muscular pain, visceral pain and inflammatory pain,epilepsy, urinary incontinence, anxiety, dependency, mania, bipolardisorders, migraine, cognitive diseases and dystonia-associateddyskinesias, which comprises administering an effective amount of atleast one compound of general formula (I) to the mammal.

The effectiveness against pain can be shown, for example, in the Bennettor Chung model (Bennett, G. J. and Xie, Y. K., A peripheralmononeuropathy in rat that produces disorders of pain sensation likethose seen in man, Pain 1988, 33(1), 87-107; Kim, S. H. and Chung, J.M., An experimental model for peripheral neuropathy produced bysegmental spinal nerve ligation in the rat, Pain 1992, 50(3), 355-363),by tail flick experiments (e.g. according to D'Amour and Smith (J.Pharm. Exp. Ther. 72, 74 79 (1941)) or by the formalin test (e.g.according to D. Dubuisson et al., Pain 1977, 4, 161-174). Theeffectiveness against epilepsy can be demonstrated, for example, in theDBA/2 mouse model (De Sarro et al., Naunyn-Schmiedeberg's Arch.Pharmacol. 2001, 363, 330-336).

The compounds according to the invention preferably have a EC₅₀ value ofnot more than 10000 nM or not more than 8000 nM, more preferably notmore than 7000 nM or not more than 6000 nM, yet more preferably not morethan 5000 nM or not more than 3000 nM, even more preferably not morethan 2000 nM or not more than 1000 nM, yet even more preferably not morethan 800 nM or not more than 700 nM, still more preferably not more than600 nM or not more than 500 nM, yet still more preferably not more than400 nM or not more than 300 nM, most preferably not more than 200 nM ornot more than 150 nM and especially not more than 120 nM or not morethan 100 nM. Methods for determining the EC₅₀ value are known to theperson skilled in the art. The EC₅₀ value is preferably determined byfluorimetry, particularly preferably as described below under“pharmacological experiments”.

The invention further provides processes for the preparation of thesubstituted compounds according to the invention.

The chemicals and reaction components used in the reactions and schemesdescribed below are available commercially or in each case can beprepared by conventional methods known to the person skilled in the art.

The reactions described can each be carried out under the conventionalconditions with which the person skilled in the art is familiar, forexample with regard to pressure or the order in which the components areadded. If appropriate, the person skilled in the art can determine theoptimum procedure under the respective conditions by carrying out simplepreliminary tests. The intermediate and end products obtained using thereactions described hereinbefore can each be purified and/or isolated,if desired and/or required, using conventional methods known to theperson skilled in the art. Suitable purifying processes are for exampleextraction processes and chromatographic processes such as columnchromatography or preparative chromatography. All of the process stepsdescribed below, as well as the respective purification and/or isolationof intermediate or end products, can be carried out partly or completelyunder an inert gas atmosphere, preferably under a nitrogen atmosphere.

If the substituted compounds according to the invention of theaforementioned general formula (I) are obtained, after preparationthereof, in the form of a mixture of their stereoisomers, preferably inthe form of their racemates or other mixtures of their variousenantiomers and/or diastereomers, they can be separated and ifappropriate isolated using conventional processes known to the personskilled in the art. Examples include chromatographic separatingprocesses, in particular liquid chromatography processes under normalpressure or under elevated pressure, preferably MPLC and HPLC processes,and also fractional crystallisation processes. These processes allowindividual enantiomers, for example diastereomeric salts formed by meansof chiral stationary phase HPLC or by means of crystallisation withchiral acids, for example (+)-tartaric acid, (−)-tartaric acid or(+)-10-camphorsulphonic acid, to be separated from one another.

General Reaction Scheme I (Synthesis of Precursors P1 and P2):

A plurality of syntheses of and synthesis paths to compounds of thegeneral formulae P1 and P2 with a very broad substitution model forresidues R², R³, R⁴, R⁵, R⁶ and R⁷ are known in the current specialistliterature. Previously unknown intermediates of the general formulae P1and P2 with similar substitution models for residues R², R³, R⁴, R⁵, R⁶and R⁷, as outlined below and whose syntheses are not described ingreater detail, can be produced by the person skilled in the artaccording to these known methods or by combination of the known methods.

General Reaction Scheme II:

In stage01, 2-quinolones ZP01 can be transformed into2-chloro-quinolines ZP02 according to methods known to the personskilled in the art, for example, by conversion with phosphoroxychloride.

In stage02 and stage11, 2-chloroquinolines ZP02 or ZP08 can betransformed into the corresponding 2-alkoxy-quinolines ZP03 (stage 02)or of the general formula (I) (stage 11) by conversion with alcoholsR⁷—OH according to methods known to the person skilled in the art, forexample, using sodium hydride.

In stage03 and stage06, esters ZP01 or ZP03 can be transformed intoacids ZP05 or ZP04, respectively, according to methods known to theperson skilled in the art, for example, using a base, for example,lithium hydroxide.

In stage04 and stage07, acids ZP04 or ZP05 can be transformed intoamides of the general formula (I) or ZP06, respectively, with aminesR¹—CH₂—NH₂ according to methods known to the person skilled in the art,for example, using a suitable coupling reagent, for example, HATU.

In stage05 and stage08, 2-hydroxy-quinolines ZP01 or ZP08, respectively,can be transformed into 2-alkoxy-quinolines ZP03 or of the generalformula (I), respectively, with compounds of the general formula R⁷—X,wherein X denotes a leaving group, for example, chlorine, bromine,methane sulphonate or p-toluene sulphonate, according to methods knownto the person skilled in the art, for example, with the addition of abase, for example, K₂CO₃.

In stage09, quinoline-2-on-3-carboxylic acids ZP05 can be transformedinto 2-chloro-quinoline-3-carboxylic acid chlorides ZP07 according tomethods known to the person skilled in the art, for example, byconversion with phosphoroxychloride.

In stage10, 2-chloro-quinoline-3-carboxylic acid chlorides ZP07 can beconverted to yield amides ZP08 with amines of the general formulaR¹—CH₂—NH₂ according to methods known to the person skilled in the art,for example, by conversion in ethanol.

In stage12 and stage 13, quinoline-3-carboxylic acid esters ZP01 orZP03, respectively, can be converted to yield amides ZP06 or of thegeneral formula (I), respectively, with amines of the general formulaR¹—CH₂—NH₂ according to methods known to the person skilled in the art,for example, with the addition of trimethylaluminium.

Thus obtained compounds of the general formula (I) can be furthertransformed to introduce and/or exchange one or more of the substituentsR¹, R², R³, R⁴ R⁵, R⁶ and R⁷ by simple derivatization reactions known tothe person skilled in the art, for example, esterification, esterformation, amide formation, etherification, ether cleavage, substitutionor cross-coupling reactions.

The invention will be described hereinafter with the aid of a number ofexamples. This description is intended merely by way of example and doesnot limit the general idea of the invention.

EXAMPLES

The indication “equivalents” (“eq.”) means molar equivalents, “RT” meansroom temperature (23±7° C.), “M” is an indication of concentration inmol/l, “aq.” means aqueous, “sat.” means saturated, “sol.” meanssolution, “conc.” means concentrated.

Further Abbreviations:

AcOH acetic acidd days

brine saturated aqueous sodium chloride solution (NaCl sol.)

CC column chromatography on silica geldba dibenzylidenacetonDCM dichloromethane

DIPEA N,N-diisopropylethylamine DMF N,N-dimethylformamide

DMSO dimethyl sulfoxideEtOAc ethyl acetateether diethyl etherEtOH ethanolh hour(s)H₂O waterHATUO-(7-aza-benzotriazol-1-yl)-N,N,N′,N′-tetramethyluroniumhexafluorophosphatem/z mass-to-charge ratioMeOH methanolMeCN acetonitrilemin minutesMS mass spectrometryMW microwaveN/A not availableNEt₃ triethylamineRS reaction solutionTHF tetrahydrofuran

TMEDA N,N,N′,N′-Tetramethylethylendiamin

Xantphos 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene

The yields of the compounds prepared were not optimized.

All temperatures are uncorrected.

All starting materials which are not explicitly described were eithercommercially available (the details of suppliers such as for exampleAcros, Avocado, Aldrich, Bachem, Fluka, Lancaster, Maybridge, Merck,Sigma, TCl, Oakwood, etc. can be found in the Symyx® Available ChemicalsDatabase of MDL, San Ramon, US, or the SciFinder® Database of the ACS,Washington D.C., US, respectively, for example) or the synthesis thereofhas already been described precisely in the specialist literature(experimental guidelines can be found in the Reaxys® Database ofElsevier, Amsterdam, NL, or the SciFinder® Database of the ACS,Washington D.C., US, respectively, for example) or can be prepared usingthe conventional methods known to the person skilled in the art.

The stationary phase used for the column chromatography was silica gel60 (0.04-0.063 mm) from E. Merck, Darmstadt.

The mixing ratios of solvents or eluents for chromatography tests arerespectively specified in volume/volume.

All the intermediate products and exemplary compounds were analyticallycharacterised by means of ¹H-NMR spectroscopy. In addition, massspectrometry tests (MS, m/z [M+H]⁺) were carried out for all theexemplary compounds and selected intermediate products.

Synthesis of Exemplary Compounds Synthesis of example 2:2-ethoxy-4-methyl-N-(thiophene-2-yl-methyl)-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide a) Synthesis of2-ethoxy-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylic acid ethylester

354 mg (2.6 mmol) K₂CO₃ was added to a solution of 700 mg (2.3 mmol)2-hydroxy-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylic acid ethylester in DMF (9 ml) and stirred for 60 min at RT. 190 μl (2.3 mmol)iodoethane was then added and the RS was stirred for a further 16 h atRT. The solution was subsequently diluted with water and EtOAc. Theorganic phase was separated, dried over MgSO₄ and concentrated in avacuum. After CC (EtOAc/hexane 1:3) of the residue, 168 mg (0.5 mmol,22%) 2-ethoxy-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylic acidethyl ester was obtained.

b) Synthesis of2-ethoxy-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylic acid

The synthesis of2-ethoxy-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylic acid isdescribed in the case of the synthesis of Example 3 Section b).

c) Synthesis of2-ethoxy-4-methyl-N-(thiophene-2-yl-methyl)-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide

53 μl (0.5 mmol) thiophene methane amine, 172 mg (0.5 mmol) HATU and 165μl (1.2 mmol) NEt₃ were added consecutively to a solution of 123 mg (0.4mmol) 2-ethoxy-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylic acidin THF (3 ml) and thereafter stirred for 16 h at RT. The solution wassubsequently diluted with EtOAc and washed with a 4N aq. NH₄CL sol., a1M aq. Na₂CO₃ sol. and brine. The organic phase was dried over MgSO₄,filtered through silica gel and concentrated in a vacuum. 116 mg (0.3mmol, 72%)2-ethoxy-4-methyl-N-(thiophene-2-yl-methyl)-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide (example 2) was obtained as a residue. MS: m/z 395.1 [M+H]⁺.

Synthesis of example 3:2-ethoxy-N-[(4-fluorophenyl)-methyl]-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide a) Synthesis of2-chloro-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylic acid ethylester

A solution of 15.0 g (50.1 mmol)2-hydroxy-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylic acid ethylester in POCl₃ (46 ml) was heated to 100° C. for 2 h. After cooling ofthe RS to RT, it was diluted with EtOAc and neutralised with a sat. aq.NaHCO₃ sol. The organic phase was separated and washed with brine, driedover MgSO₄ and concentrated in a vacuum. 15.4 g (48.5 mmol, 97%)2-chloro-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylic acid ethylester was obtained as a residue. The raw product was further convertedwithout additional purification.

b) Synthesis of2-ethoxy-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylic acid ethylester

1.2 g (17.8 mmol) sodium ethylate was added to a solution of 5.1 g (16.1mmol) 2-chloro-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylic acidethyl ester in EtOH (20 ml) at RT. The RS was subsequently heated to 60°C. for 4 h and then stirred for 16 h at RT. The solution was thendiluted with water and EtOAc. The organic phase was separated and washedwith a 4N aq. NH₄Cl sol., dried over MgSO₄ and concentrated in a vacuum.5.1 g (15.6 mmol, 97%)2-ethoxy-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylic acid ethylester was obtained as a residue. The raw product was further convertedwithout additional purification.

c) Synthesis of2-ethoxy-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylic acid

2M aq. LiOH sol. (38 ml) was added to a solution of 5.1 g (15.5 mmol)2-ethoxy-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylic acid ethylester in a MeOH/THF mixture (in each case 38 ml) and subsequently heatedto 60° C. for 16 h. The organic solvents were removed as far as possiblein a vacuum and the obtained aqueous solution was washed with EtOAc, setat pH 2 with 2M hydrochloric acid and diluted with EtOAc. The organicphase was separated and washed with brine, dried over MgSO₄ andconcentrated in a vacuum. 4.4 g (14.7 mmol, 95%)2-ethoxy-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylic acid wasobtained as a residue. The raw product was further converted withoutadditional purification.

d) Synthesis ofethoxy-N-[(4-fluorophenyl)-methyl]-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide

166 μl (1.5 mmol) 4-fluoro-benzylamine, 506 mg (1.3 mmol) HATU and 537μl (3.9 mmol) NEt₃ were added consecutively to a solution of 400 mg (1.3mmol) 2-ethoxy-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylic acidin 1,4-dioxane (11 ml) and thereafter stirred for 72 h at 80° C. Aftercooling to RT, the solution was diluted with EtOAc and washed with a 4Naq. NH₄CL sol., a 2M aq. Na₂CO₃ sol. and brine. The organic phase wasdried over MgSO₄ and concentrated in a vacuum. After CC (EA/hexane 1:3)of the residue, 432 mg (1.1 mmol, 80%)ethoxy-N-[(4-fluorophenyl)-methyl]-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide (example compound 3) was obtained. MS: m/z 407.1 [M+H]⁺.

Synthesis of example 4:N-[(3-fluorophenyl)-methyl]-2-methoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide a) Synthesis of2-hydroxy-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylic acid

2M aq. LiOH sol. (125 ml) was added to a solution of 15.0 g (50.1 mmol)2-hydroxy-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylic acid ethylester in a MeOH/THF mixture (in each case 175 ml) and the solution wassubsequently heated to 60° C. for 16 h. The solution was subsequentlyconcentrated in a vacuum. The residue was taken up with water andadjusted to pH 2 with a 2M hydrochloric acid. Extraction was thenperformed with EtOAc. The organic phase was washed with brine, driedover MgSO₄ and concentrated in a vacuum. 12.0 g (44.2 mmol, 88%)2-hydroxy-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylic acid wasobtained as a residue. The raw product was further converted withoutadditional purification.

b) Synthesis of2-chloro-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylic acidchloride

A solution of 12.0 g (44.2 mmol, 88%)2-hydroxy-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylic acid inPOCl₃ (41 ml) was stirred for 2 h at 100° C. After cooling to RT, thesolution was diluted with toluene (10 ml) and stirred for 10 min at 60°C. The solution was then concentrated in a vacuum. The residue was takenup with water and EtOAc and a 1M aq. NaHCO₃ sol. was added. The organicphase was separated, washed with water and brine, dried over MgSO₄ andconcentrated in a vacuum. 12.1 g (39.3 mmol, 89%)2-chloro-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylic acidchloride was obtained as a residue. The raw product was furtherconverted without additional purification.

c) Synthesis of2-chloro-N-(3-fluorobenzyl)-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylicacid amide

A solution of 15.6 g (50.6 mmol)2-chloro-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylic acidchloride in 1,4-dioxane (85 ml) was added in drops to a solution of 7.6g (60.8 mmol) 3-fluorobenzylamine and 10.3 ml (60.8 mmol) DIPEA in1,4-dioxane (87 ml). The RS was subsequently stirred for 60 min at RT.The solution was then diluted with water and EA. The organic phase wasseparated, washed with a 4N aq. NH₄Cl sol. and brine, dried over MgSO₄and concentrated in a vacuum. 19.4 g (48.9 mmol, 97%)2-chloro-N-(3-fluorobenzyl)-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylicacid amide was obtained as a residue. The raw product was furtherconverted without additional purification.

d) Synthesis of 2N-[(3-fluorophenyl)-methyl]-2-methoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide

150 mg (3.75 mmol, 60% in mineral oil) NaH was added to methanol (5 ml)and the solution was stirred for 15 min at RT. 496 mg (1.3 mmol)2-chloro-N-(3-fluorobenzyl)-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylicacid amide was then added and the RS was heated to 70° C. for 2 h. Thesolution was then diluted with water and EtOAc. The organic phase wasseparated, dried over MgSO₄ and concentrated in a vacuum. 435 mg (1.1mmol, 89%) 2N-[(3-fluorophenyl)-methyl]-2-methoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide (example 4) was obtained as a residue. MS: m/z 393.1 [M+H]⁺.

Synthesis of example 5:N-[(4-fluorophenyl)-methyl]-2-methoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide a) Synthesis of2-methoxy-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylic acid

A 2M aq. LiOH sol. (12 ml) was added to a solution of 1.3 g (4.0 mmol)2-chloro-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylic acid ethylester (synthesis see Example 3 Section a)) in a MeOH/THF mixture (ineach case 10 ml) and the solution was subsequently heated to 70° C. for16 h. The organic solvents were removed as far as possible in a vacuumand the obtained aqueous solution was washed with EtOAc, adjusted to pH2 with 2M hydrochloric acid and diluted with EtOAc. The organic phasewas separated and washed with brine, dried over MgSO₄ and concentratedin a vacuum. 754 mg (2.6 mmol, 66%)2-methoxy-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylic acid wasobtained as a residue. The raw product was further converted withoutadditional purification.

b) Synthesis ofN-[(4-fluorophenyl)-methyl]-2-methoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide

87 μl (0.8 mmol) 4-fluorobenzylamine, 266 mg (0.7 mmol) HATU and 281 μl(2.0 mmol) NEt₃ were added consecutively to a solution of 199 mg (0.7mmol) 2-methoxy-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylic acidin THF (5 ml) and the solution was then stirred for 72 h at RT. Thesolution was subsequently diluted with EtOAc and washed with a 4N aq.NH₄Cl sol., a 1M aq. Na₂CO₃ sol. and brine. The organic phase was driedover MgSO₄, filtered through silica gel and concentrated in a vacuum.After crystallisation (EtOAc/hexane 1:2) of the residue, 161 mg (0.4mmol, 59%)N-[(4-fluorophenyl)-methyl]-2-methoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide (example 5) was obtained. MS: m/z 393.1 [M+H]⁺.

Synthesis of example 7:N-[(3-fluorophenyl)-methyl]-2-(2-methoxy-ethoxy)-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide a) Synthesis ofN-(3-fluorobenzyl)-2-hydroxy-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylicacid amide

508 mg (4.1 mmol) 3-fluorobenzylamine, 1.4 g (3.7 mmol) HATU and 1.5 ml(10.7 mmol) NEt₃ were added consecutively to a solution of 1.0 g (3.7mmol) 2-hydroxy-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylic acid(synthesis see Example 4 Section a)) in THF (28 ml) and the solution wasthen stirred for 16 h at 50° C. The solution was subsequently dilutedwith EtOAc (30 ml). The resultant precipitate was filtered off andsuspended in a EtOAc/MeOH/DCM mixture. Concentration in a vacuum wassubsequently carried out. 1.0 g (2.6 mmol, 71%)N-(3-fluorobenzyl)-2-hydroxy-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylicacid amide was obtained as a residue. The raw product was furtherconverted without additional purification.

b) Synthesis ofN-[(3-fluorophenyl)-methyl]-2-(2-methoxy-ethoxy)-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide

120 mg (0.9 mmol) K₂CO₃ was added to a solution of 300 mg (0.8 mmol)N-(3-fluorobenzyl)-2-hydroxy-4-methyl-7-(trifluoromethyl)quinoline-3-carboxylicacid amide in DMSO (10 ml) and the solution was stirred for 60 min atRT. 121 mg (0.9 mmol) 1-bromo-2-methoxy-ethane was then added and the RSwas stirred for 16 h at RT and thereafter for 72 h at 50° C. It was thendiluted with water and EtOAc. The organic phase was separated, washedwith brine, dried over MgSO₄ and concentrated in a vacuum. After CC(EtOAc/hexane 1:3) of the residue, 72 mg (0.2 mmol, 21%)N-[(3-fluorophenyl)-methyl]-2-(2-methoxy-ethoxy)-4-methyl-7-(trifluoro-methyl)-quinoline-3-carboxylicacid amide (example 7) was obtained. MS: m/z 437.1 [M+H]⁺.

Synthesis of example 9:N-[(3-fluorophenyl)-methyl]-2-(2-hydroxy-ethoxy)-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide

9.2 ml (9.2 mmol, 1M in DCM) boron tribromide was added in drops at −50°C. to a solution of 399 mg (0.9 mmol)N-[(3-fluorophenyl)-methyl]-2-(2-methoxy-ethoxy)-4-methyl-7-(trifluoro-methyl)-quinoline-3-carboxylicacid amide (Example 7) in DCM (8 ml). The mixture was subsequentlyheated to 0° C. within 2 h and stirred for 1 h at 0° C. The mixture wasthen stirred for 1 h at 10° C. It was thereafter quenched with a 0.5 Maq. NaHCO₃ sol. and diluted with MeOH and DCM. The organic phase wasseparated and washed with a 10%-strength aq. Na₂S₂O₃ sol., dried overMgSO₄ and concentrated in a vacuum. After crystallisation (EtOAc/hexane1:1) of the residue, 109 mg (0.3 mmol, 29%)N-[(3-fluorophenyl)-methyl]-2-(2-hydroxy-ethoxy)-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide (example

9) was obtained. MS: m/z 423.1 [M+H]⁺.

Synthesis of example 12:2-ethoxy-N-[(3-fluorophenyl)-methyl]-4-methoxy-7-(trifluoremethyl)-quinoline-3-carboxylicacid amide a) Synthesis of2-ethoxy-N-(3-fluorobenzyl)-4-hydroxy-7-(trifluoromethyl)quinoline-3-carboxylicacid amide

1.5 ml (3.0 mmol, 2M in toluene) trimethylaluminium and 350 μl (3.0mmol) 3-fluorobenzylamine were added consecutively at RT to a solutionof 500 mg (1.5 mmol)2-ethoxy-4-hydroxy-7-(trifluoromethyl)quinoline-3-carboxylic acid ethylester in toluene (10 ml). The RS was subsequently heated to 80° C. for 4h. The mixture was subsequently diluted with water and extracted withEtOAc. The organic phase was washed with water and brine, dried overNa₂SO₄ and concentrated in a vacuum. After CC (EtOAc/hexane 1:9) of theresidue, 250 mg (0.6 mmol, 41%)2-ethoxy-N-(3-fluorobenzyl)-4-hydroxy-7-(trifluoromethyl)quinoline-3-carboxylicacid amide was obtained.

b) Synthesis of2-ethoxy-N-[(3-fluorophenyl)-methyl]-4-methoxy-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide

300 mg (2.2 mmol) K₂CO₃ and 0.9 ml (14.6 mmol) methyliodide were addedto a solution of 300 mg (0.7 mmol)2-ethoxy-N-(3-fluorobenzyl)-4-hydroxy-7-(trifluoro-methyl)quinoline-3-carboxylicacid amide in DMF (5 ml) and the mixture was stirred for 16 h at RT. Themixture was subsequently diluted with water and extracted with EtOAc.The organic phase was washed with water and brine, dried over Na₂SO₄ andconcentrated in a vacuum. After CC (EtOAc/hexane 1:12) of the residue,240 mg (0.6 mmol, 81%)2-ethoxy-N-[(3-fluorophenyl)-methyl]-4-methoxy-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide (example 12) was obtained. MS: m/z 423.1 [M+H]⁺.

Synthesis of example 13:N-[(3-fluorophenyl)-methyl]-2,4-dimethoxy-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide a) Synthesis ofN-(3-fluorobenzyl)-2,4-dihydroxy-7-(trifluoromethyl)quinoline-3-carboxylicacid amide

2.0 ml (17.3 mmol) 3-fluorobenzylamine was added to a suspension of 1.3g (4.3 mmol) 2,4-dihydroxy-7-(trifluoromethyl)quinoline-3-carboxylicacid ethyl ester in EtOH (50 ml) and the mixture was heated to 90° C.for 3 h. Concentration in a vacuum was subsequently carried out. AfterCC (DCM) of the residue, 1.6 g (4.2 mmol, 98%)N-(3-fluorobenzyl)-2,4-dihydroxy-7-(trifluoromethyl)quinoline-3-carboxylicacid amide was obtained.

b) Synthesis ofN-[(3-fluorophenyl)-methyl]-2,4-dimethoxy-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide

1.8 g (6.6 mmol) Ag₂CO₃ was added to a solution of 500 mg (1.3 mmol)N-(3-fluorobenzyl)-2,4-dihydroxy-7-(trifluoromethyl)-quinoline-3-carboxylicacid in DCM (15 ml) and the solution was stirred for 10 min at RT. 820μl (13.2 mmol) methyliodide was then added and the RS was stirred for afurther 20 h at RT. Filtering off was then performed and the filtratewas concentrated in a vacuum. After CC (EtOAc/hexane 1:12) of theresidue, 51 mg (0.1 mmol, 9%)N-[(3-fluorophenyl)-methyl]-2,4-dimethoxy-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide (example 13) was obtained. MS: m/z 409.1 [M+H]⁺.

Synthesis of example 36:7-Cyano-2-ethoxy-N-[(3-fluorophenyl)-methyl]-4-methyl-quinoline-3-carboxylicacid amide

To a solution of 600 mg (1.44 mmol)7-bromo-2-ethoxy-N-[(3-fluorophenyl)-methyl]-4-methyl-quinoline-3-carboxylicacid amide (example 32) in DMF (3 mL) were added 46 μL (0.32 mmol)TMEDA, 102 mg (0.86 mmol) zinc cyanide, 2 mg (0.007 mmol) Pd₂dba₃ andXantphos. The reaction solution was degasses and flushed with nitrogenthree times and then heated in MW to 160° C. for 4 min. After cooling toRT the mixture was filtered through celite and it was washed withdichloromethane. The combined organic layers were concentrated in vacuo.After CC (EtOAc/hexane 1:2) of the residue, 310 mg (0.85 mmol, 59%)7-Cyano-2-ethoxy-N-[(3-fluorophenyl)-methyl]-4-methyl-quinoline-3-carboxylicacid amide (example 36) were obtained. MS: m/z 364.1 [M+H]⁺.

Synthesis of example 42:N-[(3-Fluoro-2-hydroxy-phenyl)-methyl]-2-methoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide a) Synthesis ofN-[(3-Fluoro-2-methoxy-phenyl)-methyl]-2-chloro-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide

The synthesis was performed analogous to the synthesis described forexample 4 section c)

b) Synthesis ofN-[(3-Fluoro-2-hydroxy-phenyl)-methyl]-2-chloro-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide

A solution of 278 mg (0.65 mmol)N-[(3-fluoro-2-methoxy-phenyl)-methyl]-2-chloro-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide in DCM (13 ml) was cooled to −30° C. and subsequently treatedwith 6.5 ml (6.5 mmol, 1M in DCM) tribromoborane at this temperature.After stirring at −5° C. for 3 h, the reaction mixture was stirred at 0°C. for 16 h, followed by quenching with a 1M aq, NaHCO₃ sol. The layerswere separated and the aqueous layer was extracted with EtOAc. Thecombined organic layers were dried washed brine, dried over MgSO₄. Afterfiltering and concentration in vacuum 241 mg (0.56 mmol, 87%)N-[(3-Fluoro-2-hydroxy-phenyl)-methyl]-2-chloro-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide were obtained.

c) Synthesis ofN-[(3-Fluoro-2-hydroxy-phenyl)-methyl]-2-methoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide

Reaction of 238 mg (0.57 mmol)N-[(3-fluoro-2-hydroxy-phenyl)-methyl]-2-chloro-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide following the procedure as described for example 4 section d)provided 45 mg (0.11 mmol, 19%)N-[(3-Fluoro-2-hydroxy-phenyl)-methyl]-2-methoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide (example 42). MS: m/z 409.1 [M+H]⁺.

Synthesis of example 46:N-[(3-Fluoro-2-hydroxy-phenyl)-methyl]-2-methoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide a) Synthesis of7-fluoro-2-hydroxy-4-methylquinoline-3-carboxylic acid ethyl ester

The synthesis was performed analogous to the synthesis described forexample 2 section a)

b) Synthesis of 7-fluoro-2-methoxy-4-methylquinoline-3-carboxylic acidethyl ester

To a stirred solution of 2.30 g (9.24 mmol)7-fluoro-2-hydroxy-4-methylquinoline-3-carboxylic acid ethyl ester inDCM (60 ml) were added 6.36 g (23.1 mmol) Ag₂CO₃ and 1.44 ml (23.1 mmol)iodomethane at RT. The reaction mixture was stirred at RT for 16 h. Thenthe mixture was filtered through celite and the filtrate wasconcentrated in vacuum. After CC (EtOAc/hexane 1:4) of the residue, 1.50g (5.70 mmol, 62%) 7-fluoro-2-methoxy-4-methylquinoline-3-carboxylicacid ethyl ester were obtained.

c) Synthesis of7-Fluoro-N-[(4-fluorophenyl)-methyl]-2-methoxy-4-methyl-quinoline-3-carboxylicacid amide

To a stirred solution of 400 mg (1.52 mmol)7-fluoro-2-methoxy-4-methylquinoline-3-carboxylic acid ethyl ester intoluene (10 ml) were added 3.04 ml (2M solution in toluene, 6.1 mmol)Me₃Al at RT followed by the addition of 700 μl (6.1 mmol)4-fluorobenzylamine. The reaction mixture was heated at 110° C. for 16h. Then the reaction was quenched with water (10 ml) and extracted withEtOAc (3×20 ml). The combined organic layers were washed with water (20ml), brine (20 ml), dried over Na₂SO₄ and concentrated in vacuum. AfterCC (EtOAc/hexane 1:4) of the residue, 160 mg (0.47 mmol, 31%)7-fluoro-N-[(4-fluorophenyl)-methyl]-2-methoxy-4-methyl-quinoline-3-carboxylicacid amide (example 46) were obtained. MS: m/z 343.1 [M+H]⁺.

Synthesis of Further Examples

The synthesis of further examples was carried out according to themethods already described. Table 1 shows which compound was producedaccording to which method. It is evident to the person skilled in theart which educts and reagents were used in each case.

TABLE 1 Preparation analogous to MS m/z Example chemical name example[M + H]⁺ 1 N-(3,3-Dimethyl-butyl)-2-methoxy-4-methyl-7- 3 369.2(trifluoromethyl)-quinoline-3-carboxylic acid amide 62-Ethoxy-N-[(3-fluorophenyl)-methyl]-4-methyl- 3 407.17-(trifluoromethyl)-quinoline-3-carboxylic acid amide 8N-[(4-Fluorophenyl)-methyl]-2-(2-methoxy- 7 437.1ethoxy)-4-methyl-7-(trifluoromethyl)-quinoline- 3-carboxylic acid amide10 N-[(3-Fluorophenyl)-methyl]-2-isopropoxy-4- 4 421.1methyl-7-(trifluoromethyl)-quinoline-3- carboxylic acid amide 11N-[(4-Fluorophenyl)-methyl]-2-isopropoxy-4- 4 421.1methyl-7-(trifluoromethyl)-quinoline-3- carboxylic acid amide 142-Ethoxy-N-[(4-fluorophenyl)-methyl]-4- 12 423.1methoxy-7-(trifluoromethyl)-quinoline-3- carboxylic acid amide 152-Ethoxy-6,7-difluoro-N-[(3-fluorophenyl)- 12 391.1methyl]-4-methoxy-quinoline-3-carboxylic acid amide 16N-[(4-Fluorophenyl)-methyl]-2,4-dimethoxy-7- 13 409.1(trifluoromethyl)-quinoline-3-carboxylic acid amide 176,7-Difluoro-N-[(3-fluorophenyl)-methyl]-2,4- 13 377.1dimethoxy-quinoline-3-carboxylic acid amide 187-Fluoro-N-[(3-fluorophenyl)-methyl]-2- 2 343.1methoxy-4-methyl-quinoline-3-carboxylic acid amide 19N-[(3-Fluoro-4-methyl-phenyl)-methyl]-2- 3 407.1methoxy-4-methyl-7-(trifluoromethyl)- quinoline-3-carboxylic acid amide20 2-Ethoxy-N-[(3-fluoro-4-methyl-phenyl)- 3 421.1methyl]-4-methyl-7-(trifluoromethyl)-quinoline- 3-carboxylic acid amide21 2-Methoxy-4-methyl-N-(m-tolyl-methyl)-7- 3 389.1(trifluoromethyl)-quinoline-3-carboxylic acid amide 222-Ethoxy-4-methyl-N-(m-tolyl-methyl)-7- 3 403.2(trifluoromethyl)-quinoline-3-carboxylic acid amide 23N-[(4-Fluoro-3-methyl-phenyl)-methyl]-2- 3 407.1methoxy-4-methyl-7-(trifluoromethyl)- quinoline-3-carboxylic acid amide24 2-Ethoxy-N-[(4-fluoro-3-methyl-phenyl)- 3 421.1methyl]-4-methyl-7-(trifluoromethyl)-quinoline- 3-carboxylic acid amide25 2-Methoxy-4-methyl-N-(p-tolyl-methyl)-7- 3 389.1(trifluoromethyl)-quinoline-3-carboxylic acid amide 262-Ethoxy-4-methyl-N-(p-tolyl-methyl)-7- 3 403.2(trifluoromethyl)-quinoline-3-carboxylic acid amide 272-Ethoxy-4-methyl-N-(4-methyl-pentyl)-7- 3 383.2(trifluoromethyl)-quinoline-3-carboxylic acid amide 282-Methoxy-4-methyl-N-(4-methyl-pentyl)-7- 3 369.2(trifluoromethyl)-quinoline-3-carboxylic acid amide 29N-(4,4-Dimethyl-pentyl)-2-methoxy-4-methyl- 3 383.27-(trifluoromethyl)-quinoline-3-carboxylic acid amide 30N-(4,4-Dimethyl-pentyl)-2-ethoxy-4-methyl-7- 3 397.2(trifluoromethyl)-quinoline-3-carboxylic acid amide 317-Bromo-2-ethoxy-N-[(4-fluorophenyl)-methyl]- 3 417.14-methyl-quinoline-3-carboxylic acid amide 327-Bromo-2-ethoxy-N-[(3-fluorophenyl)-methyl]- 3 417.14-methyl-quinoline-3-carboxylic acid amide 337-Bromo-N-[(3-fluorophenyl)-methyl]-2- 3 403.0methoxy-4-methyl-quinoline-3-carboxylic acid amide 347-Bromo-N-[(4-fluorophenyl)-methyl]-2- 3 403.0methoxy-4-methyl-quinoline-3-carboxylic acid amide 357-Cyano-2-ethoxy-N-[(4-fluorophenyl)-methyl]- 36 364.14-methyl-quinoline-3-carboxylic acid amide 377-Cyano-N-[(3-fluorophenyl)-methyl]-2- 36 350.1methoxy-4-methyl-quinoline-3-carboxylic acid amide 387-Cyano-N-[(4-fluorophenyl)-methyl]-2- 36 350.1methoxy-4-methyl-quinoline-3-carboxylic acid amide 39N-[(3-Fluoro-2-methoxy-phenyl)-methyl]-2- 3 423.1methoxy-4-methyl-7-(trifluoromethyl)- quinoline-3-carboxylic acid amide40 N-[(3-Fluoro-5-methoxy-phenyl)-methyl]-2- 3 423.1methoxy-4-methyl-7-(trifluoromethyl)- quinoline-3-carboxylic acid amide41 N-[(5-Fluoro-2-methoxy-phenyl)-methyl]-2- 3 423.1methoxy-4-methyl-7-(trifluoromethyl)- quinoline-3-carboxylic acid amide43 N-[(3-Fluoro-5-hydroxy-phenyl)-methyl]-2- 42 409.1methoxy-4-methyl-7-(trifluoromethyl)- quinoline-3-carboxylic acid amide44 N-[(5-Fluoro-2-hydroxy-phenyl)-methyl]-2- 42 409.1methoxy-4-methyl-7-(trifluoromethyl)- quinoline-3-carboxylic acid amide45 N-[(3-Fluoro-4-hydroxy-phenyl)-methyl]-2- 42 409.1methoxy-4-methyl-7-(trifluoromethyl)- quinoline-3-carboxylic acid amide47 5,7-Difluoro-N-[(3-fluorophenyl)-methyl]-2- 46 361.1methoxy-4-methyl-quinoline-3-carboxylic acid amide 486,7-Difluoro-N-[(3-fluorophenyl)-methyl]-2- 46 361.1methoxy-4-methyl-quinoline-3-carboxylic acid amide 497,8-Difluoro-N-[(3-fluorophenyl)-methyl]-2- 46 361.1methoxy-4-methyl-quinoline-3-carboxylic acid amide 50N-[(3-Fluorophenyl)-methyl]-4-methyl-2-(2,2,2- 4 461.1trifluoro-ethoxy)-7-(trifluoromethyl)-quinoline- 3-carboxylic acid amide51 N-[(3-Fluorophenyl)-methyl]-2-methoxy-4- 4 379.1(trifluoromethyl)-quinoline-3-carboxylic acid amide 522-Ethoxy-N-[(3-fluorophenyl)-methyl]-4- 4 393.1(trifluoromethyl)-quinoline-3-carboxylic acid amide 53N-[(3-Fluorophenyl)-methyl]-2-isopropoxy-4- 4 407.1(trifluoromethyl)-quinoline-3-carboxylic acid amide

Pharmacological Experiments Method I. Fluorescence Assay Using a VoltageSensitive Dye (Fluorimetry)

Human CHO—K1 cells expressing KCNQ2/3 channels are cultivated adherentlyat 37° C., 5% CO₂ and 95% humidity in cell culture bottles (e.g. 80 cm²TC flasks, Nunc) with DMEM-high glucose (Sigma Aldrich, D7777) including10% FCS (PAN Biotech, e.g. 3302-P270521) or alternatively MEM AlphaMedium (1×, liquid, Invitrogen, #22571), 10% fetal calf serum (FCS)(Invitrogen, #10270-106, heat-inactivated) and the necessary selectionantibiotics.

Before being sown out for the measurements, the cells are washed with1×DPBS buffer Ca²⁺/Mg²⁺-free (e.g. Invitrogen, #14190-094) and detachedfrom the bottom of the culture vessel by using Accutase (PAALaboratories, #L11-007) (incubation with Accutase for 15 min at 37° C.).The cell number is determined using a CASY™ cell counter (TCC, SchärfeSystem). Depending on the optimal density for each individual cell line,20,000-30,000 cells/well/100 μl are seeded onto 96-well Corning™CellBIND™ assay plates (Flat Clear Bottom Black Polystyrene Microplates,#3340). Freshly seeded cells are then left to settle for one hour atroom temperature, followed by incubation for 24 hours at 37° C., 5% CO₂and 95% humidity.

The voltage-sensitive fluorescent dye from the Membrane Potential AssayKit (Red™ Bulk format part R8123 for FLIPR, MDS AnalyticalTechnologies™) is prepared by dissolving the contents of one vesselMembrane Potential Assay Kit Red Component A in 200 ml of extracellularbuffer (ES buffer, 120 mM NaCl, 1 mM KCl, 10 mM HEPES, 2 mM CaCl₂, 2 mMMgCl₂, 10 mM glucose; pH 7.4). After removal of the nutrient medium, thecells are washed once with 200 μl of ES buffer, then loaded for 45 minat room temperature in 100 μl of dye solution in the dark.

Fluorescence measurements are carried out in a BMG Labtech FLUOstar™,BMG Labtech NOVOstar™ or BMG Labtech POLARstar™ instrument (525 nmexcitation, 560 nm emission, Bottom Read mode). After incubation withthe dye, 50 μl of the test substances in the desired concentrations, or50 μl of ES buffer for control purposes, are applied to the wells of theassay plate and incubated for 30 min at room temperature while beingshielded from light. The fluorescence intensity of the dye is thenmeasured for 5 min and the fluorescence value F₁ of each well is thusdetermined at a given, constant time. 15 μl of a KCl solution are thenadded to each well (final concentration of potassium ions 92 mM). Thechange in fluorescence intensity is subsequently monitored until all therelevant values have been obtained (mainly 5-30 min). At a given timepost KCl application, a fluorescence value F₂ is determined, in thiscase at the time of the fluorescence peak.

For calculation, the fluorescence intensity F₂ is corrected for thefluorescence intensity F₁, and the activity (ΔF/F) of the targetcompound on the potassium channel is determined as follows:

${\left( \frac{F_{2} - F_{1}}{F_{1}} \right) \times 100} = {\frac{\Delta \; F}{F}(\%)}$

In order to determine whether a substance has agonistic activity,

$\frac{\Delta \; F}{F}$

can be related to

$\left( \frac{\Delta \; F}{F} \right)_{K}$

of control wells.

$\left( \frac{\Delta \; F}{F} \right)_{K}$

is determined by adding to the well only the buffer solution instead ofthe test substance, determining the value F_(1K) of the fluorescenceintensity, adding the potassium ions as described above, and measuring avalue F_(2K) of the fluorescence intensity. F_(2K) and F_(1K) are thencalculated as follows:

${\left( \frac{F_{2K} - F_{1K}}{F_{1K}} \right) \times 100} = {\left( \frac{\Delta \; F}{F} \right)_{K}(\%)}$

A substance has an agonistic activity on the potassium channel if

$\frac{\Delta \; F}{F}$

is greater than

${{\left( \frac{\Delta \; F}{F} \right)_{K}\text{:}\mspace{11mu} \frac{\Delta \; F}{F}}\rangle}\left( \frac{\Delta \; F}{F} \right)_{K}$

Independently of the comparison of

$\frac{\Delta \; F}{F}$

with

$\left( \frac{\Delta \; F}{F} \right)_{K}$

it is possible to conclude that a target compound has agonistic activityif

$\frac{\Delta \; F}{F}$

increases dose dependently.

Calculations of EC₅₀ and IC₅₀ values are carried out with the aid of‘Prism v4.0’ software (Graph Pad Software™).

Method II. Low-Intensity Tail Flick Test (Rat)

In the low-intensity tail flick test, the determination of theantinociceptive effect of the compounds according to the inventiontowards an acute noxious thermal stimulus is carried out by measuringthe withdrawal reflex of the rat tail (tail flick) in response to aradiant heat beam (analgesia meter; model 2011 of the company RhemaLabortechnik, Hofheim, Germany) according to the method described byD'Amour and Smith (J. Pharm. Exp. Ther. 72, 74 79 (1941). To this end,the rats were placed in a plexiglas restrainer, and a low-intensityradiant heat beam (48° C.) was focused onto the dorsal surface of thetail root. The stimulus intensity was adjusted to result in a meanpre-drug control withdrawal latency of about 7 s, thus also allowing asupraspinal modulation of the spinally mediated acute nociceptivereflex. A cutoff time of 30 s was applied to avoid tissue damage. MaleSprague-Dawley rats (Janvier, Le Genest St. Isle, Frankreich) withweights of 200-250 g were used. 10 rats were used per group. Beforeadministration of a compound according to the invention, the animalswere pre-tested twice in the course of five minutes and the mean ofthese measurements was calculated as the pre-test mean. Theantinociceptive effect was determined at 20, 40 and 60 min after peroralcompound administration. The antinociceptive effect was calculated basedon the increase in the tail withdrawal latency according to thefollowing formula and is expressed as percentage of the maximum possibleeffect (MPE [%]):

MPE=[(T ₁ −T ₀)/(T ₂ −T ₀)]*100

In this, T₀ is the control latency time before and T₁ the latency timeafter administration of the compound, T₂ is the cutoff time and MPE isthe maximum possible effect. Employing variant analysis (repeatedmeasures ANOVA) allowed testing of statistically significant differencesbetween the compounds according to the invention and the vehicle group.The significance level was set to p≦0.05. To determine the dosedependency, the particular compound according to the invention wasadministered in 3-5 logarithmically increasing doses, including athreshold dose and a maximum effective dose, and the ED₅₀ values weredetermined with the aid of regression analysis. The ED₅₀ calculation wasperformed at the time of maximum efficacy (usually 20 min afteradministration of the compounds).

Pharmacological Data

The pharmacological effects of the compounds according to the inventionwere determined as described hereinbefore (pharmacological experiments,methods I and II respectively).

The corresponding pharmacological data are summarized in Table 2.

TABLE 2 Fluorimetry % efficacy Fluorimetry Low intensity tail flick,(retigabine = EC₅₀ rat, peroral, ED₅₀ or MPE Example 100%) [nM] (dose)[mg/kg] 1 57 2 175 64 3 122 39 2.5 4 105 73 6.7 5 122 57 34% (6.81)  6132 58 67% (4.64)  7 92 96 10.0  8 94 143 22% (10.00) 9 119 390 10 17587 3.8 11 164 52 12 170 104 27% (4.64)  13 147 136 10% (10.00) 14 155 7515 181 106 16 159 106 74% (10.00) 17 147 218 18 62 340 19 99 92 20 14672 24% (10.00) 21 71 67 22 111 58 20% (10.00) 23 73 62 24 108 53 17%(6.81)  25 96 182 26 117 131 27 173 84 28 184 81 29 244 28 28% (10.00)30 214 50 35 112 82 32% (6.81)  36 105 56 37 85 261 38 74 143 39 10 4015 41 140 1541 42 137 123 43 9 44 173 79 45 87 2057 46 59 299 47 43 4896 315 49 70 229 50 108 25 24% @ 10.00 51 40 52 67 205 53 84 108

1. A substituted compound of general formula (I)

wherein R¹ represents a C₁₋₁₀-aliphatic residue, unsubstituted or mono-or polysubstituted; a C₃₋₁₀-cycloaliphatic residue or a 3 to 10 memberedheterocycloaliphatic residue, in each case unsubstituted or mono- orpolysubstituted and in each case optionally bridged via a C₁₋₈ aliphaticgroup, which in turn may be unsubstituted or mono- or polysubstituted;aryl or heteroaryl, in each case unsubstituted or mono- orpolysubstituted and in each case optionally bridged via a C₁₋₈ aliphaticgroup, which in turn may be unsubstituted or mono- or polysubstituted;R² represents H; F; Cl; Br; I; CN; CF₃; C(═O)H; NO₂; OCF₃; SCF₃; aC₁₋₄-aliphatic residue, a C(═O)—C₁₋₄ aliphatic residue, a C(═O)—O—C₁₋₄aliphatic residue, a C(═O)—NH—C₁₋₄ aliphatic residue, a C(═O)—N(C₁₋₄aliphatic residue)₂, wherein the C₁₋₄ aliphatic residue may be in eachcase be unsubstituted or mono- or polysubstituted; a O—C₁₋₄-aliphaticresidue, a O—C(═O)—C₁₋₄-aliphatic residue, a S—C₁₋₄-aliphatic residue, aS(═O)₂—C₁₋₄-aliphatic residue, a S(═O)₂—O—C₁₋₄-aliphatic residue,wherein the C₁₋₄ aliphatic residue may be in each case be unsubstitutedor mono- or polysubstituted; a C₃₋₆-cycloaliphatic residue or a 3 to 6membered heterocycloaliphatic residue, in each case unsubstituted ormono- or polysubstituted and in each case optionally bridged via a C₁₋₄aliphatic group, which in turn may be unsubstituted or mono- orpolysubstituted; R³, R⁴, R⁵ and R⁶ each independently of one anotherrepresent H; F; Cl; Br; I; CN; CF₃; C(═O)H; C(═O)—OH; C(═O)—NH₂; SCF₃;S(═O)₂—OH; NO₂; OCF₃; a C₁₋₄-aliphatic residue, a C(═O)—C₁₋₄ aliphaticresidue, a C(═O)—O—C₁₋₄ aliphatic residue, a C(═O)—NH—C₁₋₄ aliphaticresidue, a C(═O)—N(C₁₋₄ aliphatic residue)₂, wherein the C₁₋₄ aliphaticresidue may be in each case be unsubstituted or mono- orpolysubstituted; a O—C₁₋₄-aliphatic residue, a O—C(═O)—C₁₋₄-aliphaticresidue, a S—C₁₋₄-aliphatic residue, a S(═O)₂—C₁₋₄-aliphatic residue, aS(═O)₂—O—C₁₋₄-aliphatic residue, wherein the C₁₋₄ aliphatic residue maybe in each case be unsubstituted or mono- or polysubstituted; a NH(C₁₋₄aliphatic residue), a N(C₁₋₄ aliphatic residue)₂, a NH—C(═O)—C₁₋₄aliphatic residue, a NH—S(═O)₂—C₁₋₄-aliphatic residue, a N(C₁₋₄aliphatic residue)-C(═O)—C₁₋₄ aliphatic residue, or a N(C₁₋₄ aliphaticresidue)-S(═O)₂—C₁₋₄ aliphatic residue, wherein the C₁₋₄ aliphaticresidue may in each case be unsubstituted or mono- or polysubstituted; aC₃₋₆-cycloaliphatic residue or a 3 to 6 membered heterocycloaliphaticresidue, in each case unsubstituted or mono- or polysubstituted and ineach case optionally bridged via a C₁₋₄ aliphatic group, which in turnmay be unsubstituted or mono- or polysubstituted; R⁷ represents aC₁₋₁₀-aliphatic residue, unsubstituted or mono- or polysubstituted; aC₃₋₁₀-cycloaliphatic residue or a 3 to 10 membered heterocycloaliphaticresidue, in each case unsubstituted or mono- or polysubstituted and ineach case optionally bridged via a C₁₋₈ aliphatic group, which in turnmay be unsubstituted or mono- or polysubstituted; on the condition thatif R⁷ denotes a 3 to 10 membered heterocycloaliphatic residue, the 3 to10 membered heterocycloaliphatic residue is linked via a carbon atom, inwhich an “aliphatic group” and “aliphatic residue” can in each case bebranched or unbranched, saturated or unsaturated, in which a“cycloaliphatic residue” and a “heterocycloaliphatic residue” can ineach case be saturated or unsaturated, in which “mono- orpolysubstituted” with respect to an “aliphatic group” and an “aliphaticresidue” relates, with respect to the corresponding residues or groups,to the substitution of one or more hydrogen atoms each independently ofone another by at least one substituent selected from the groupconsisting of F, Cl, Br, I, NO₂, NH₂, an NH(C₁₋₄ aliphatic residue), anN(C₁₋₄ aliphatic residue)₂, a NH—C(═O)—C₁₋₄ aliphatic residue, aNH—S(═O)₂—C₁₋₄ aliphatic residue, ═O, OH, OCF₃, a O—C₁₋₄-aliphaticresidue, a O—C(═O)—C₁₋₄-aliphatic residue, SH, SCF₃, a S—C₁₋₄-aliphaticresidue, S(═O)₂OH, a S(═O)₂—C₁₋₄-aliphatic residue, aS(═O)₂—O—C₁₋₄-aliphatic residue, a S(═O)₂—NH—C₁₋₄-aliphatic residue, CN,CF₃, CHO, COOH, a C₁₋₄-aliphatic residue, a C(═O)—C₁₋₄-aliphaticresidue, a C(═O)—O—C₁₋₄-aliphatic residue, a C₃₋₆-cycloaliphaticresidue, a 3 to 6 membered heterocycloaliphatic residue, C(═O)—NH₂, aC(═O)—NH(C₁₋₄ aliphatic residue), and a C(═O)—N(C₁₋₄ aliphaticresidue)₂; in which “mono- or polysubstituted” with respect to a“cycloaliphatic residue” and a “heterocycloaliphatic residue” relates,with respect to the corresponding residues, to the substitution of oneor more hydrogen atoms each independently of one another by at least onesubstituent selected from the group consisting of F, Cl, Br, I, NO₂,NH₂, an NH(C₁₋₄ aliphatic residue), an N(C₁₋₄ aliphatic residue)₂, aNH—C(═O)—C₁₋₄ aliphatic residue, a NH—S(═O)₂—C₁₋₄ aliphatic residue, ═O,OH, OCF₃, a O—C₁₋₄-aliphatic residue, a O—C(═O)—C₁₋₄-aliphatic residue,SH, SCF₃, a S—C₁₋₄-aliphatic residue, S(═O)₂OH, a S(═O)₂—C₁₋₄-aliphaticresidue, a S(═O)₂—O—C₁₋₄-aliphatic residue, a S(═O)₂—NH—C₁₋₄-aliphaticresidue, CN, CF₃, CHO, COOH, a C₁₋₄-aliphatic residue, aC(═O)—C₁₋₄-aliphatic residue, a C(═O)—O—C₁₋₄-aliphatic residue, aC₃₋₆-cycloaliphatic residue, a 3 to 6 membered heterocycloaliphaticresidue, C(═O)—NH₂, a C(═O)—NH(C₁₋₄ aliphatic residue), and aC(═O)—N(C₁₋₄ aliphatic residue)₂; in which “mono- or polysubstituted”with respect to “aryl” and a “heteroaryl” relates, with respect to thecorresponding residues, to the substitution of one or more hydrogenatoms each independently of one another by at least one substituentselected from the group consisting of F, Cl, Br, I, NO₂, NH₂,

an NH(C₁₋₄ aliphatic residue), an N(C₁₋₄ aliphatic residue)₂, anNH—C(═O)—C₁₋₄ aliphatic residue, an NH—S(═O)₂—C₁₋₄ aliphatic residue,OH, OCF₃, a O—C₁₋₄-aliphatic residue, a O—C(═O)—C₁₋₄-aliphatic residue,SH, SCF₃, a S—C₁₋₄-aliphatic residue, S(═O)₂OH, a S(═O)₂—C₁₋₄-aliphaticresidue, a S(═O)₂—O—C₁₋₄-aliphatic residue, a S(═O)₂—NH—C₁₋₄-aliphaticresidue, CN, CF₃, C(═O)H, C(═O)OH, a C₁₋₄-aliphatic residue, aC(═O)—C₁₋₄-aliphatic residue, a C(═O)—O—C₁₋₄-aliphatic residue, aC₃₋₆-cycloaliphatic residue, a 3 to 6 membered heterocycloaliphaticresidue, benzyl, aryl, heteroaryl, C(═O)—NH₂, a C(═O)—NH(C₁₋₄ aliphaticresidue), and a C(═O)—N(C₁₋₄ aliphatic residue)₂; in the form of thefree compounds, the racemate, the enantiomers, diastereomers, mixturesof the enantiomers or diastereomers in any mixing ratio, or of anindividual enantiomer or diastereomer, or in the form of the salts ofphysiologically acceptable acids or bases.
 2. The compound according toclaim 1, wherein R¹ denotes a C₁₋₁₀-aliphatic residue, unsubstituted ormono- or polysubstituted with at least one substituent selected from thegroup consisting of F, Cl, Br, I, NO₂, NH₂, an NH(C₁₋₄ aliphaticresidue), an N(C₁₋₄ aliphatic residue)₂, OH, ═O, an O—C₁₋₄-aliphaticresidue, OCF₃, SH, SCF₃, a S—C₁₋₄-aliphatic residue, CF₃, CN, aC₁₋₄-aliphatic residue and C(═O)—OH, wherein the C₁₋₄-aliphatic residuein each case may be unsubstituted or mono- or polysubstituted with atleast one substituent selected from the group consisting of F, Cl, Br,I, OH, OCF₃, CF₃ and an unsubstituted O—C₁₋₄-aliphatic residue, ordenotes a C₃₋₁₀-cycloaliphatic residue or a 3 to 10 memberedheterocycloaliphatic residue, in each case unsubstituted or mono- orpolysubstituted with at least one substituent selected from the groupconsisting of F, Cl, Br, I, NO₂, NH₂, an NH(C₁₋₄ aliphatic residue), anN(C₁₋₄ aliphatic residue)₂, OH, ═O, an O—C₁₋₄ aliphatic residue, OCF₃,SH, SCF₃, a S—C₁₋₄ aliphatic residue, CF₃, CN, a C₁₋₄-aliphatic residue,C(═O)—OH, a C₃₋₆ cycloaliphatic residue, and a 3 to 6 memberedheterocycloaliphatic residue, wherein the C₁₋₄-aliphatic residue in eachcase may be unsubstituted or mono- or polysubstituted with at least onesubstituent selected from the group consisting of F, Cl, Br, I, OH,OCF₃, CF₃ and an unsubstituted O—C₁₋₄-aliphatic residue, and wherein theC₃₋₆ cycloaliphatic residue and the 3 to 6 membered heterocycloaliphaticresidue may in each case may be unsubstituted or mono- orpolysubstituted with at least one substituent selected from the groupconsisting of F, Cl, Br, I, NO₂, NH₂, an NH(C₁₋₄ aliphatic residue), anN(C₁₋₄ aliphatic residue)₂, OH, ═O, an O—C₁₋₄ aliphatic residue, OCF₃,SH, SCF₃, a S—C₁₋₄ aliphatic residue, CF₃, CN, a C₁₋₄-aliphatic residueand C(═O)—OH, and wherein the C₃₋₁₀-cycloaliphatic residue or the 3 to10 membered heterocycloaliphatic residue may in each case optionallybridged via a C₁₋₈ aliphatic group, which in turn may be unsubstitutedor mono- or polysubstituted with at least one substituent selected fromthe group consisting of F, Cl, Br, I, NO₂, NH₂, an NH(C₁₋₄ aliphaticresidue), an N(C₁₋₄ aliphatic residue)₂, OH, ═O, an O—C₁₋₄ aliphaticresidue, OCF₃, SH, SCF₃, a S—C₁₋₄ aliphatic residue, CF₃, CN, aC₁₋₄-aliphatic residue and C(═O)—OH, or denotes an aryl or heteroaryl,in each case unsubstituted or mono- or polysubstituted with at least onesubstituent selected from the group consisting of F, Cl, Br, I, NO₂,NH₂, an NH(C₁₋₄ aliphatic residue), an N(C₁₋₄ aliphatic residue)₂, OH,an O—C₁₋₄ aliphatic residue, OCF₃, SH, SCF₃, a S—C₁₋₄ aliphatic residue,CF₃, CN, a C₁₋₄-aliphatic residue, C(═O)—OH, C(═O)—CH₃, C(═O)—C₂H₅,C(═O)—O—CH₃ and C(═O)—O—C₂H₅, a C₃₋₆ cycloaliphatic residue, a 3 to 6membered heterocycloaliphatic residue,

 benzyl, phenyl, thienyl, pyridyl, furyl, thiazolyl and oxazolyl,wherein the C₁₋₄-aliphatic residue in each case may be unsubstituted ormono- or polysubstituted with at least one substituent selected from thegroup consisting of F, Cl, Br, I, OH, OCF₃, CF₃ and an unsubstitutedO—C₁₋₄-aliphatic residue, and wherein benzyl, phenyl, thienyl, pyridyl,furyl, thiazolyl and oxazolyl may in each case may be unsubstituted ormono- or polysubstituted with at least one substituent selected from thegroup consisting of F, Cl, Br, I, NO₂, NH₂, an NH(C₁₋₄ aliphaticresidue), an N(C₁₋₄ aliphatic residue)₂, OH, an O—C₁₋₄ aliphaticresidue, OCF₃, O—CH₂—OH, O—CH₂—O—CH₃, SH, SCF₃, a S—C₁₋₄ aliphaticresidue, CF₃, CN, a C₁₋₄-aliphatic residue, C(═O)—OH, C(═O)—CH₃,C(═O)—C₂H₅, C(═O)—O—CH₃ and C(═O)—O—C₂H₅, and wherein the C₃₋₆cycloaliphatic residue and the 3 to 6 membered heterocycloaliphaticresidue may in each case may be unsubstituted or mono- orpolysubstituted with at least one substituent selected from the groupconsisting of F, Cl, Br, I, NO₂, NH₂, an NH(C₁₋₄ aliphatic residue), anN(C₁₋₄ aliphatic residue)₂, OH, ═O, an O—C₁₋₄ aliphatic residue, OCF₃,SH, SCF₃, a S—C₁₋₄ aliphatic residue, CF₃, CN, a C₁₋₄-aliphatic residueand C(═O)—OH, and wherein the aryl or the heteroaryl residue may in eachcase be optionally bridged via a C₁₋₈ aliphatic group, which in turn maybe unsubstituted or mono- or polysubstituted with at least onesubstituent selected from the group consisting of F, Cl, Br, I, NO₂,NH₂, an NH(C₁₋₄ aliphatic residue), an N(C₁₋₄ aliphatic residue)₂, OH,═O, an O—C₁₋₄ aliphatic residue, OCF₃, SH, SCF₃, a S—C₁₋₄ aliphaticresidue, CF₃, CN and C(═O)—OH, R² represents H; F; Cl; Br; I; CN; CF₃;NO₂; OCF₃; SCF₃; a C₁₋₄-aliphatic residue, a S—C₁₋₄-aliphatic residue, aO—C₁₋₄-aliphatic residue, wherein the C₁₋₄ aliphatic residue may be ineach case be unsubstituted or mono- or polysubstituted; aC₃₋₆-cycloaliphatic residue or a 3 to 6 membered heterocycloaliphaticresidue, in each case unsubstituted or mono- or polysubstituted and ineach case optionally bridged via a C₁₋₄ aliphatic group, which in turnmay be unsubstituted or mono- or polysubstituted, R³, R⁴, R⁵ and R⁶ eachindependently of one another represent H; F; Cl; Br; I; CN; CF₃; OCF₃;SCF₃; C(═O)H; C(═O)—OH; C(═O)—NH₂; S(═O)₂—OH; NO₂; a C₁₋₄-aliphaticresidue, a C(═O)—C₁₋₄ aliphatic residue, a C(═O)—O—C₁₋₄ aliphaticresidue, a C(═O)—NH—C₁₋₄ aliphatic residue, a C(═O)—N(C₁₋₄ aliphaticresidue)₂, a O—C₁₋₄-aliphatic residue, a O—C(═O)—C₁₋₄-aliphatic residue,a S—C₁₋₄-aliphatic residue, a S(═O)₂—C₁₋₄-aliphatic residue, a NH(C₁₋₄aliphatic residue), a N(C₁₋₄ aliphatic residue)₂, a NH—C(═O)—C₁₋₄aliphatic residue, and a NH—S(═O)₂—C₁₋₄-aliphatic residue, wherein theC₁₋₄-aliphatic residue in each case may be unsubstituted or mono- orpolysubstituted with at least one substituent selected from the groupconsisting of F, Cl, Br, I, ═O, OH, and a O—C₁₋₄-aliphatic residue; aO₃₋₆-cycloaliphatic residue or a 3 to 6 membered heterocycloaliphaticresidue, in each case unsubstituted or mono- or polysubstituted with atleast one substituent selected from the group consisting of F, Cl, Br,I, ═O, OH, a C₁₋₄-aliphatic residue and a O—C₁₋₄-aliphatic residue, andin each case optionally bridged via an unsubstituted C₁₋₄ aliphaticgroup, R⁷ denotes a C₁₋₁₀-aliphatic residue, unsubstituted or mono- orpolysubstituted with at least one substituent selected from the groupconsisting of F, Cl, Br, I, NO₂, NH₂, an NH(C₁₋₄ aliphatic residue), anN(C₁₋₄ aliphatic residue)₂, OH, ═O, an O—C₁₋₄-aliphatic residue, OCF₃,SH, SCF₃, a S—C₁₋₄-aliphatic residue, CF₃, CN, a C₁₋₄-aliphatic residueand C(═O)—OH, wherein the C₁₋₄-aliphatic residue in each case may beunsubstituted or mono- or polysubstituted with at least one substituentselected from the group consisting of F, Cl, Br, I, OH, OCF₃, CF₃ and anunsubstituted O—C₁₋₄-aliphatic residue, or denotes aC₃₋₁₀-cycloaliphatic residue or a 3 to 10 membered heterocycloaliphaticresidue, in each case unsubstituted or mono- or polysubstituted with atleast one substituent selected from the group consisting of F, Cl, Br,I, NO₂, NH₂, an NH(C₁₋₄ aliphatic residue), an N(C₁₋₄ aliphaticresidue)₂, OH, ═O, an O—C₁₋₄ aliphatic residue, OCF₃, SH, SCF₃, a S—C₁₋₄aliphatic residue, CF₃, CN, a C₁₋₄-aliphatic residue, C(═O)—OH, a C₃₋₆cycloaliphatic residue, and a 3 to 6 membered heterocycloaliphaticresidue, wherein the C₁₋₄-aliphatic residue in each case may beunsubstituted or mono- or polysubstituted with at least one substituentselected from the group consisting of F, Cl, Br, I, OH, OCF₃, CF₃ and anunsubstituted O—C₁₋₄-aliphatic residue, and wherein the C₃₋₆cycloaliphatic residue and the 3 to 6 membered heterocycloaliphaticresidue may in each case may be unsubstituted or mono- orpolysubstituted with at least one substituent selected from the groupconsisting of F, Cl, Br, I, NO₂, NH₂, an NH(C₁₋₄ aliphatic residue), anN(C₁₋₄ aliphatic residue)₂, OH, ═O, an O—C₁₋₄ aliphatic residue, OCF₃,SH, SCF₃, a S—C₁₋₄ aliphatic residue, CF₃, CN, a C₁₋₄-aliphatic residueand C(═O)—OH, and wherein the C₃₋₁₀-cycloaliphatic residue or the 3 to10 membered heterocycloaliphatic residue may in each case optionallybridged via a C₁₋₈ aliphatic group, which in turn may be unsubstitutedor mono- or polysubstituted with at least one substituent selected fromthe group consisting of F, Cl, Br, I, NO₂, NH₂, an NH(C₁₋₄ aliphaticresidue), an N(C₁₋₄ aliphatic residue)₂, OH, ═O, an O—C₁₋₄ aliphaticresidue, OCF₃, SH, SCF₃, a S—C₁₋₄ aliphatic residue, CF₃, CN, aC₁₋₄-aliphatic residue and C(═O)—OH, on the condition that if R⁷ denotesa 3 to 10 membered heterocycloaliphatic residue, the 3 to 10 memberedheterocycloaliphatic residue is linked via a carbon atom.
 3. Thecompound according to claim 1, wherein R² represents H; F; Cl; Br; I;CN; CF₃; NO₂; OCF₃; SCF₃; a C₁₋₄-aliphatic residue, a S—C₁₋₄-aliphaticresidue, a O—C₁₋₄-aliphatic residue, wherein the C₁₋₄-aliphatic residuein each case may be unsubstituted or mono- or polysubstituted with atleast one substituent selected from the group consisting of F, Cl, Br,I, ═O, OH, and an unsubstituted O—C₁₋₄-aliphatic residue, aC₃₋₆-cycloaliphatic residue or a 3 to 6 membered heterocycloaliphaticresidue, in each case unsubstituted or mono- or polysubstituted with atleast one substituent selected from the group consisting of F, Cl, Br,I, ═O, OH, a C₁₋₄-aliphatic residue and a O—C₁₋₄-aliphatic residue,wherein the C₁₋₄-aliphatic residue in each case may be unsubstituted ormono- or polysubstituted with at least one substituent selected from thegroup consisting of F, Cl, Br, I, ═O, OH, and an unsubstitutedO—C₁₋₄-aliphatic residue, and wherein the C₃₋₆-cycloaliphatic residue orthe 3 to 6 membered heterocycloaliphatic residue may in each case beoptionally bridged via a C₁₋₄ aliphatic group, which in turn may beunsubstituted or mono- or polysubstituted with at least one substituentselected from the group consisting of F, Cl, Br, I, ═O, OH, anunsubstituted C₁₋₄-aliphatic residue and an unsubstitutedO—C₁₋₄-aliphatic residue.
 4. The compound according to claim 1, whereinR³, R⁴, R⁵ and R⁶ each independently of one another represent H; F; Cl;Br; I; CN; CF₃; OCF₃; SCF₃; C(═O)H; C(═O)—OH; C(═O)—NH₂; S(═O)₂—OH; NO₂;a C₁₋₄-aliphatic residue, a C(═O)—C₁₋₄ aliphatic residue, a C(═O)—O—C₁₋₄aliphatic residue, a O—C₁₋₄-aliphatic residue, a O—C(═O)—C₁₋₄-aliphaticresidue, a S—C₁₋₄-aliphatic residue, a S(═O)₂—C₁₋₄-aliphatic residue,wherein the C₁₋₄-aliphatic residue in each case may be unsubstituted ormono- or polysubstituted with at least one substituent selected from thegroup consisting of F, Cl, Br, I, ═O, OH, and a O—C₁₋₄-aliphaticresidue; a C₃₋₆-cycloaliphatic residue or a 3 to 6 memberedheterocycloaliphatic residue, in each case unsubstituted or mono- orpolysubstituted with at least one substituent selected from the groupconsisting of F, Cl, Br, I, ═O, OH, a C₁₋₄-aliphatic residue and aO—C₁₋₄-aliphatic residue, and in each case optionally bridged via anunsubstituted C₁₋₄ aliphatic group.
 5. The compound according to claim1, wherein R³, R⁴, R⁵ and R⁶ each independently of one another areselected from the group consisting of H; F; Cl; Br; I; NO₂; CF₃; CN;OCF₃; SCF₃; a (C═O)—C₁₋₄ aliphatic residue, a C₁₋₄ aliphatic residue,O—C₁₋₄ aliphatic residue, a S—C₁₋₄ aliphatic residue, wherein theC₁₋₄-aliphatic residue in each case may be unsubstituted or mono- orpolysubstituted with at least one substituent selected from the groupconsisting of F, Cl, and O—CH₃.
 6. The compound according to claim 1,wherein at least one of R³, R⁴, R⁵ and R⁶ is ≠H.
 7. The compoundaccording to claim 1, wherein R¹ represents the partial structure (T1)

wherein m denotes 0, 1, 2, 3 or 4, R^(8a) and R^(8b) each independentlyof one another represent H, F, Cl, Br, I, NO₂, NH₂, a NH(C₁₋₄ aliphaticresidue), an N(C₁₋₄ aliphatic residue)₂, OH, an O—C₁₋₄ aliphaticresidue, OCF₃, SH, SCF₃, a S—C₁₋₄ aliphatic residue, CF₃, CN, a C₁₋₄aliphatic residue or C(═O)—OH, or together denote ═O, R^(8c) denotes aC₁₋₄ aliphatic residue, unsubstituted or mono- or polysubstituted withat least one substituent selected from the group consisting of F, Cl,Br, I, NO₂, NH₂, an NH(C₁₋₄ aliphatic residue), an N(C₁₋₄ aliphaticresidue)₂, OH, ═O, an O—C₁₋₄ aliphatic residue, OCF₃, SH, SCF₃, a S—C₁₋₄aliphatic residue, CF₃, CN, a C₁₋₄-aliphatic residue and C(═O)—OH, ordenotes a C₃₋₁₀-cycloaliphatic residue or a 3 to 10 memberedheterocycloaliphatic residue, in each case unsubstituted or mono- orpolysubstituted with at least one substituent selected from the groupconsisting of F, Cl, Br, I, NO₂, NH₂, an NH(C₁₋₄ aliphatic residue), anN(C₁₋₄ aliphatic residue)₂, OH, ═O, an O—C₁₋₄ aliphatic residue, OCF₃,SH, SCF₃, a S—C₁₋₄ aliphatic residue, CF₃, CN, a C₁₋₄-aliphatic residue,C(═O)—OH, a C₃₋₆ cycloaliphatic residue and a 3 to 6 memberedheterocycloaliphatic residue, wherein the C₁₋₄-aliphatic residue in eachcase may be unsubstituted or mono- or polysubstituted with at least onesubstituent selected from the group consisting of F, Cl, Br, I, OH,OCF₃, CF₃ and an unsubstituted O—C₁₋₄-aliphatic residue, and wherein theC₃₋₆ cycloaliphatic residue and the 3 to 6 membered heterocycloaliphaticresidue may in each case may be unsubstituted or mono- orpolysubstituted with at least one substituent selected from the groupconsisting of F, Cl, Br, I, NO₂, NH₂, an NH(C₁₋₄ aliphatic residue), anN(C₁₋₄ aliphatic residue)₂, OH, ═O, an O—C₁₋₄ aliphatic residue, OCF₃,SH, SCF₃, a S—C₁₋₄ aliphatic residue, CF₃, CN, a C₁₋₄-aliphatic residueand C(═O)—OH, or denotes an aryl or heteroaryl, in each caseunsubstituted or mono- or polysubstituted with at least one substituentselected from the group consisting of F, Cl, Br, I, NO₂, NH₂, an NH(C₁₋₄aliphatic residue), an N(C₁₋₄ aliphatic residue)₂, OH, an O—C₁₋₄aliphatic residue, OCF₃, SH, SCF₃, a S—C₁₋₄ aliphatic residue, CF₃, CN,a C₁₋₄-aliphatic residue, C(═O)—OH, C(═O)—CH₃, C(═O)—C₂H₅, C(═O)—O—CH₃and C(═O)—O—C₂H₅, a C₃₋₆ cycloaliphatic residue, a 3 to 6 memberedheterocycloaliphatic residue,

 benzyl, phenyl, thienyl, pyridyl, furyl, thiazolyl and oxazolyl,wherein the C₁₋₄-aliphatic residue in each case may be unsubstituted ormono- or polysubstituted with at least one substituent selected from thegroup consisting of F, Cl, Br, I, OH, OCF₃, CF₃ and an unsubstitutedO—C₁₋₄-aliphatic residue, and wherein benzyl, phenyl, thienyl, pyridyl,furyl, thiazolyl and oxazolyl may in each case may be unsubstituted ormono- or polysubstituted with at least one substituent selected from thegroup consisting of F, Cl, Br, I, NO₂, NH₂, an NH(C₁₋₄ aliphaticresidue), an N(C₁₋₄ aliphatic residue)₂, OH, an O—C₁₋₄ aliphaticresidue, OCF₃, SH, SCF₃, a S—C₁₋₄ aliphatic residue, CF₃, CN, aC₁₋₄-aliphatic residue, C(═O)—OH, C(═O)—CH₃, C(═O)—C₂H₅, C(═O)—O—CH₃ andC(═O)—O—C₂H₅, and wherein the C₃₋₆ cycloaliphatic residue and the 3 to 6membered heterocycloaliphatic residue may in each case may beunsubstituted or mono- or polysubstituted with at least one substituentselected from the group consisting of F, Cl, Br, I, NO₂, NH₂, an NH(C₁₋₄aliphatic residue), an N(C₁₋₄ aliphatic residue)₂, OH, ═O, an O—C₁₋₄aliphatic residue, OCF₃, SH, SCF₃, a S—C₁₋₄ aliphatic residue, CF₃, CN,a C₁₋₄-aliphatic residue and C(═O)—OH.
 8. The compound according toclaim 1, wherein R¹ represents the partial structure (T1),

wherein m denotes 0, 1, or 2, R^(8a) and R^(8b) each independently ofone another represent H, F, Cl, Br, I, an O—C₁₋₄ aliphatic residue or aC₁₋₄ aliphatic residue, R^(8c) denotes a C₁₋₄ aliphatic residue,unsubstituted or mono- or polysubstituted with at least one substituentselected from the group consisting of F, Cl, Br, I, an O—C₁₋₄ aliphaticresidue, CF₃, and a C₁₋₄-aliphatic residue, wherein the C₁₋₄-aliphaticresidue in each case may be unsubstituted or mono- or polysubstitutedwith at least one substituent selected from the group consisting of F,Cl, CF₃ and an unsubstituted O—C₁₋₄-aliphatic residue, or denotes aC₃₋₁₀-cycloaliphatic residue or a 3 to 10 membered heterocycloaliphaticresidue, in each case unsubstituted or mono- or polysubstituted with atleast one substituent selected from the group consisting of F, Cl, Br,I, an O—C₁₋₄ aliphatic residue, CF₃, and a C₁₋₄-aliphatic residue,wherein the C₁₋₄-aliphatic residue in each case may be unsubstituted ormono- or polysubstituted with at least one substituent selected from thegroup consisting of F, Cl, CF₃ and an unsubstituted O—C₁₋₄-aliphaticresidue, or denotes an aryl or heteroaryl, in each case unsubstituted ormono- or polysubstituted with at least one substituent selected from thegroup consisting of F, Cl, Br, I, OH, an O—C₁₋₄ aliphatic residue, OCF₃,CF₃, CN, a C₁₋₄-aliphatic residue, C(═O)—CH₃, C(═O)—C₂H₅, C(═O)—O—CH₃and C(═O)—O—C₂H₅, a C₃₋₆ cycloaliphatic residue, a 3 to 6 memberedheterocycloaliphatic residue, benzyl, phenyl, thienyl or pyridyl,wherein benzyl, phenyl, thienyl and pyridyl, may in each case may beunsubstituted or mono- or polysubstituted with at least one substituentselected from the group consisting of F, Cl, Br, I, OH, an O—C₁₋₄aliphatic residue, OCF₃, CF₃, CN, a C₁₋₄-aliphatic residue, C(═O)—CH₃,C(═O)—C₂H₅, C(═O)—O—CH₃ and C(═O)—O—C₂H₅, and wherein the C₃₋₆cycloaliphatic residue and the 3 to 6 membered heterocycloaliphaticresidue may in each case may be unsubstituted or mono- orpolysubstituted with at least one substituent selected from the groupconsisting of F, Cl, Br, I, OH, ═O, an O—C₁₋₄ aliphatic residue, OCF₃,CF₃ a C₁₋₄-aliphatic residue and C(═O)—OH.
 9. The compound according toclaim 1, wherein R⁷ denotes a C₁₋₁₀-aliphatic residue, unsubstituted ormono- or polysubstituted with at least one substituent selected from thegroup consisting of F, Cl, Br, I, NO₂, OH, ═O, an O—C₁₋₄-aliphaticresidue, OCF₃, SH, SCF₃, a S—C₁₋₄-aliphatic residue, aC(═O)—O—C₁₋₄-aliphatic residue, CF₃, CN, and a C₁₋₄-aliphatic residuewherein the C₁₋₄-aliphatic residue in each case may be unsubstituted ormono- or polysubstituted with at least one substituent selected from thegroup consisting of F, Cl, Br, I, OH, OCF₃, CF₃ and an unsubstitutedO—C₁₋₄-aliphatic residue, or denotes a C₃₋₁₀-cycloaliphatic residue or a3 to 10 membered heterocycloaliphatic residue, in each caseunsubstituted or mono- or polysubstituted with at least one substituentselected from the group consisting of F, Cl, Br, I, NO₂, OH, ═O, anO—C₁₋₄ aliphatic residue, OCF₃, SH, SCF₃, a S—C₁₋₄ aliphatic residue, aC(═O)—O—C₁₋₄-aliphatic residue, CF₃, CN, a C₁₋₄-aliphatic residue, aC₃₋₆ cycloaliphatic residue, and a 3 to 6 membered heterocycloaliphaticresidue, wherein the C₁₋₄-aliphatic residue in each case may beunsubstituted or mono- or polysubstituted with at least one substituentselected from the group consisting of F, Cl, Br, I, OH, OCF₃, CF₃ and anunsubstituted O—C₁₋₄-aliphatic residue, and wherein the C₃₋₆cycloaliphatic residue and the 3 to 6 membered heterocycloaliphaticresidue may in each case may be unsubstituted or mono- orpolysubstituted with at least one substituent selected from the groupconsisting of F, Cl, Br, I, NO₂, OH, ═O, an O—C₁₋₄ aliphatic residue,OCF₃, SH, SCF₃, a S—C₁₋₄ aliphatic residue, CF₃, CN, and aC₁₋₄-aliphatic residue, and wherein the C₃₋₁₀-cycloaliphatic residue orthe 3 to 10 membered heterocycloaliphatic residue may in each caseoptionally bridged via a C₁₋₈ aliphatic group, which in turn may beunsubstituted or mono- or polysubstituted with at least one substituentselected from the group consisting of F, Cl, Br, I, NO₂, OH, ═O, anO—C₁₋₄ aliphatic residue, a C(═O)—O—C₁₋₄-aliphatic residue, OCF₃, SH,SCF₃, a S—C₁₋₄ aliphatic residue, CF₃, CN, and a C₁₋₄-aliphatic residue.on the condition that if R⁷ denotes a 3 to 10 memberedheterocycloaliphatic residue, the 3 to 10 membered heterocycloaliphaticresidue is linked via a carbon atom.
 10. The compound according to claim1, wherein R⁷ denotes a C₁₋₈-aliphatic residue, unsubstituted or mono-or polysubstituted with at least one substituent selected from the groupconsisting of F, Cl, Br, I, OH, ═O, an O—C₁₋₄-aliphatic residue, aC(═O)—O—C₁₋₄-aliphatic residue, OCF₃, SH, SCF₃, a S—C₁₋₄-aliphaticresidue, CF₃, and a C₁₋₄-aliphatic residue wherein the C₁₋₄-aliphaticresidue in each case may be unsubstituted or mono- or polysubstitutedwith at least one substituent selected from the group consisting of F,Cl, Br, I, OH, CF₃ and an unsubstituted O—C₁₋₄-aliphatic residue, ordenotes a C₃₋₁₀-cycloaliphatic residue or a 3 to 10 memberedheterocycloaliphatic residue, in each case unsubstituted or mono- orpolysubstituted with at least one substituent selected from the groupconsisting of F, Cl, Br, I, OH, ═O, an O—C₁₋₄ aliphatic residue, OCF₃,SCF₃, a S—C₁₋₄ aliphatic residue, a C(═O)—O—C₁₋₄-aliphatic residue, CF₃,and a C₁₋₄-aliphatic residue, wherein the C₁₋₄-aliphatic residue in eachcase may be unsubstituted or mono- or polysubstituted with at least onesubstituent selected from the group consisting of F, Cl, Br, I, OH,OCF₃, CF₃ and an unsubstituted O—C₁₋₄-aliphatic residue, and wherein theC₃₋₁₀-cycloaliphatic residue or the 3 to 10 memberedheterocycloaliphatic residue is bridged via a unsubstituted C₁₋₈aliphatic group.
 11. The compound according to claim 7, wherein R¹represents the partial structure (T1),

wherein m is 0, 1 or 2 and R^(8a) and R^(8b) each independently of oneanother represent H, F, a O—C₁₋₄ aliphatic residue or a C₁₋₄ aliphaticresidue; R^(8c) denotes a C₁₋₄ aliphatic residue, unsubstituted or mono-or polysubstituted with at least one substituent selected from the groupconsisting of F, Cl, Br, I, an unsubstituted O—C₁₋₄ aliphatic residue,CF₃, and an unsubstituted C₁₋₄-aliphatic residue, or denotes aC₃₋₁₀-cycloaliphatic residue or a 3 to 10 membered heterocycloaliphaticresidue, in each case unsubstituted or mono- or polysubstituted with atleast one substituent selected from the group consisting of F, Cl, Br,I, an unsubstituted O—C₁₋₄ aliphatic residue, CF₃, and an unsubstitutedC₁₋₄-aliphatic residue, or wherein m is 0, R^(8a) and R^(8b) eachindependently of one another represent H, F, a O—C₁₋₄ aliphatic residueor a C₁₋₄ aliphatic residue; and R^(8c) denotes an aryl or heteroaryl,in each case unsubstituted or mono- or polysubstituted with at least onesubstituent selected from the group consisting of F, Cl, Br, I, OH, anO—C₁₋₄ aliphatic residue, OCF₃, CF₃, CN, a C₁₋₄-aliphatic residue,C(═O)—CH₃, C(═O)—C₂H₅, C(═O)—O—CH₃, C(═O)—O—C₂H₅ and phenyl, whereinphenyl may be unsubstituted or mono- or polysubstituted with at leastone substituent selected from the group consisting of F, Cl, Br, I, OH,an O—C₁₋₄ aliphatic residue, OCF₃, CF₃, CN, a C₁₋₄-aliphatic residue,C(═O)—CH₃, C(═O)—C₂H₅, C(═O)—O—CH₃ and C(═O)—O—C₂H₅, R² is selected fromthe group consisting of H; F; Cl; CF₃; CH₃; C₂H₅, iso-propyl;cyclopropyl; and O—CH₃; R³, R⁴, R⁵ and R⁶ are each independently of oneanother selected from the group consisting of H; F; Cl; Br; CF₃; CN;OCF₃ and NO₂; R⁷ denotes a C₁₋₆-aliphatic residue, unsubstituted ormono- or polysubstituted with at least one substituent selected from thegroup consisting of F, Cl, Br, I, OH, ═O, an O—C₁₋₄-aliphatic residue, aC(═O)—O—C₁₋₄-aliphatic residue, OCF₃, SH, SCF₃, a S—C₁₋₄-aliphaticresidue, CF₃, and a C₁₋₄-aliphatic residue, wherein the C₁₋₄-aliphaticresidue in each case is unsubstituted.
 12. The compound according toclaim 1, wherein the compound is selected from the group consisting of:1N-(3,3-dimethyl-butyl)-2-methoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide; 22-ethoxy-4-methyl-N-(thiophene-2-yl-methyl)-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide; 32-ethoxy-N-[(4-fluorophenyl)-methyl]-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide; 4N-[(3-fluorophenyl)-methyl]-2-methoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide; 5N-[(4-fluorophenyl)-methyl]-2-methoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide; 62-ethoxy-N-[(3-fluorophenyl)-methyl]-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide; 7N-[(3-fluorophenyl)-methyl]-2-(2-methoxy-ethoxy)-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide; 8N-[(4-fluorophenyl)-methyl]-2-(2-methoxy-ethoxy)-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide; 9N-[(3-fluorophenyl)-methyl]-2-(2-hydroxy-ethoxy)-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide; 10N-[(3-fluorophenyl)-methyl]-2-isopropoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide; 11N-[(4-fluorophenyl)-methyl]-2-isopropoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide; 122-ethoxy-N-[(3-fluorophenyl)-methyl]-4-methoxy-7-(trifluoremethyl)-quinoline-3-carboxylicacid amide; 13N-[(3-fluorophenyl)-methyl]-2,4-dimethoxy-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide; 142-ethoxy-N-[(4-fluorophenyl)-methyl]-4-methoxy-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide; 152-ethoxy-6,7-difluoro-N-[(3-fluorophenyl)-methyl]-4-methoxy-quinoline-3-carboxylicacid amide; 16N-[(4-fluorophenyl)-methyl]-2,4-dimethoxy-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide; 176,7-difluoro-N-[(3-fluorophenyl)-methyl]-2,4-dimethoxy-quinoline-3-carboxylicacid amide; 187-fluoro-N-[(3-fluorophenyl)-methyl]-2-methoxy-4-methyl-quinoline-3-carboxylicacid amide; 19N-[(3-fluoro-4-methyl-phenyl)-methyl]-2-methoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide; 202-ethoxy-N-[(3-fluoro-4-methyl-phenyl)-methyl]-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide; 212-methoxy-4-methyl-N-(m-tolyl-methyl)-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide; 222-ethoxy-4-methyl-N-(m-tolyl-methyl)-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide; 23N-[(4-fluoro-3-methyl-phenyl)-methyl]-2-methoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide; 242-ethoxy-N-[(4-fluoro-3-methyl-phenyl)-methyl]-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide; 252-methoxy-4-methyl-N-(p-tolyl-methyl)-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide; 262-ethoxy-4-methyl-N-(p-tolyl-methyl)-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide; 272-ethoxy-4-methyl-N-(4-methyl-pentyl)-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide; 282-methoxy-4-methyl-N-(4-methyl-pentyl)-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide; 29N-(4,4-dimethyl-pentyl)-2-methoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide; 30N-(4,4-dimethyl-pentyl)-2-ethoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide; 317-bromo-2-ethoxy-N-[(4-fluorophenyl)methyl]-4-methyl-quinoline-3-carboxylicacid amide; 327-bromo-2-ethoxy-N-[(3-fluorophenyl)-methyl]-4-methyl-quinoline-3-carboxylicacid amide; 337-bromo-N-[(3-fluorophenyl)-methyl]-2-methoxy-4-methyl-quinoline-3-carboxylicacid amide; 347-bromo-N-[(4-fluorophenyl)-methyl]-2-methoxy-4-methyl-quinoline-3-carboxylicacid amide; 357-cyano-2-ethoxy-N-[(4-fluorophenyl)-methyl]-4-methyl-quinoline-3-carboxylicacid amide; 367-cyano-2-ethoxy-N-[(3-fluorophenyl)-methyl]-4-methyl-quinoline-3-carboxylicacid amide; 377-cyano-N-[(3-fluorophenyl)-methyl]-2-methoxy-4-methyl-quinoline-3-carboxylicacid amide; 387-cyano-N-[(4-fluorophenyl)-methyl]-2-methoxy-4-methyl-quinoline-3-carboxylicacid amide; 39N-[(3-fluoro-2-methoxy-phenyl)-methyl]-2-methoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide; 40N-[(3-fluoro-5-methoxy-phenyl)-methyl]-2-methoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide; 41N-[(5-fluoro-2-methoxy-phenyl)-methyl]-2-methoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide; 42N-[(3-fluoro-2-hydroxy-phenyl)-methyl]-2-methoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide; 43N-[(3-fluoro-5-hydroxy-phenyl)-methyl]-2-methoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide; 44N-[(5-fluoro-2-hydroxy-phenyl)-methyl]-2-methoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide; 45N-[(3-fluoro-4-hydroxy-phenyl)-methyl]-2-methoxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide; 467-fluoro-N-[(4-fluorophenyl)-methyl]-2-methoxy-4-methyl-quinoline-3-carboxylicacid amide: 475,7-difluoro-N-[(3-fluorophenyl)-methyl]-2-methoxy-4-methyl-quinoline-3-carboxylicacid amide; 486,7-difluoro-N-[(3-fluorophenyl)-methyl]-2-methoxy-4-methyl-quinoline-3-carboxylicacid amide; 497,8-difluoro-N-[(3-fluorophenyl)-methyl]-2-methoxy-4-methyl-quinoline-3-carboxylicacid amide; 50N-[(3-fluorophenyl)-methyl]-4-methyl-2-(2,2,2-trifluoro-ethoxy)-7-(trifluoromethyl)-quinoline-3-carboxylicacid amide; 51N-[(3-fluorophenyl)-methyl]-2-methoxy-4-(trifluoromethyl)-quinoline-3-carboxylicacid amide; 522-ethoxy-N-[(3-fluorophenyl)-methyl]-4-(trifluoromethyl)-quinoline-3-carboxylicacid amide; and 53N-[(3-fluorophenyl)-methyl]-2-isopropoxy-4-(trifluoromethyl)-quinoline-3-carboxylicacid amide; respectively in the form of the free compounds; theracemate; the enantiomers, diastereomers, mixtures of the enantiomers ordiastereomers in any mixing ratio or of an individual enantiomer ordiastereomer; or in the form of the salts of physiologically acceptableacids or bases.
 13. A pharmaceutical composition comprising at least onecompound according to claim 1 in the form of the free compounds; theracemate; the enantiomers, diastereomers, mixtures of the enantiomers ordiastereomers in any mixing ratio or of an individual enantiomer ordiastereomer; or in the form of the salts of physiologically acceptableacids or bases, and optionally at least one pharmaceutically acceptableauxiliary and/or optionally at least one further active ingredient. 14.A method for the treatment or prophylaxis of a disorder and/or diseasein a mammal in need thereof, wherein said disorder and/or disease ismediated, at least in part, by KCNQ2/3 K⁺ channels, said methodcomprising administering an effective amount therefor of at least onecompound according to claim 1 to the mammal.
 15. The method according toclaim 14, wherein the disorder and/or disease is selected from the groupconsisting of pain, epilepsy, urinary incontinence, anxiety, dependency,mania, bipolar disorders, migraine, cognitive diseases anddystonia-associated dyskinesias.